This site contains scientific and medical information. Intended for use by medical and healthcare professionals only.
>Medical Professionals Only
Medical Professionals Only
Researcher(s):
Armuzzi A et al.
Research Unit(s):
Department of Internal Medicine, Catholic University, Rome, Italy
Department of Hygiene, Catholic University, Rome, Italy
Department of Medical Pathology, Catholic University, Rome, Italy
Human Nutrition, Tor Vergata University, Rome, Italy
Title of research:
The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2001;15:163-169
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2001.00923.x/abstract
Abstract/Summary:
Background:
One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations.
Aim:
To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden.
Methods:
Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability.
Results:
Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1–0.9; relative risk=0.3, 95% CI: 0.1–0.9; relative risk=0.5, 95% CI: 0.2–0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04).
Conclusions:
Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.
Researcher(s):
Arvola T et al.
Research Unit(s):
Medical School, University of Tampere and the Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Departments of Physiology and Clinical Nutrition, University of Kuopio, Kuopio, Finland;
Health Care Center, Tampere, Finland
Departments of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Department of Virology, University of Helsinki, Helsinki, Finland
Department of Pediatrics, University of Turku, Turku, Finland
Title of research:
Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhoea in children with respiratory infections: a randomized study.
Scientific/Medical Publication:
Pediatrics 1999;104(5):e64
Reference:
http://pediatrics.aappublications.org/content/104/5/e64.long
Abstract/Summary:
Objectives:
Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea.
Methods:
Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12.8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment.
The patients were randomized to receive placebo or 2 × 1010 colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, β-glucosidase, and β-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, β-glucuronidase, and β-glucosidase.
Results:
On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (χ2 = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was −11% (−21%–0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3–6) and the duration of diarrhea (mean: 4 days; range: 2–8).
The activities of fecal urease and β-glucuronidase, but not β-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. The decrease in urease and β-glucuronidase activities was reversible in patients with no diarrhea, but in patients with diarrhea, the modifications in gut microflora were more profound and prolonged. The activities of the three enzymes were normalized within 3 weeks, evidenced by stable enzyme activities in samples collected 3 weeks, 1 month, and 3 months after the beginning of the antimicrobial treatment, compared with those obtained before treatment.
Discussion:
In the present study, after a single antimicrobial treatment, the incidence of diarrhea was 16%. The higher incidence of antibiotic-associated diarrhea in previous reports may be attributable to a recent antimicrobial therapy that disturbs intestinal flora and exposes to complications. Also, in the present study, changes in the metabolic activity of the intestinal flora were observed, evidenced by a transient decline in fecal enzyme activities.
Different probiotic preparations, including lactobacilli, are recommended frequently to prevent antibiotic-associated diarrhea. Although probiotics have been shown to be efficient in the prevention and the treatment of viral gastroenteritis, their usefulness during antimicrobial therapy in children has not been elucidated before. We observed that the administration of Lactobacillus GG to children receiving antimicrobial therapy for respiratory infection reduced the incidence of antibiotic-associated diarrhea to one third. The beneficial effect may be mediated by a number of functions of probiotics, ie, production of antimicrobial substances, local competition of adhesion receptors and nutrients, and stimulation of intestinal antigen specific and nonspecific immune responses.
Conclusion:
A probiotic strain, Lactobacillus GG, is effective in the prevention of diarrhea in children receiving antimicrobial treatment to respiratory infections.
Researcher(s):
Cresci G et al.
Research Unit(s):
Cleveland Clinic, Cleveland, Ohio
Georgia Health Sciences University, Augusta, Georgia
Title of research:
Lactobacillus GG and Tributyrin supplementation reduce antibiotic-induced intestinal injury.
Scientific/Medical Publication:
J Parenter Enteral Nutr 2013;37:763-774
Reference:
http://pen.sagepub.com/content/37/6/763.abstract
Abstract/Summary:
Background:
Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes.
Methods:
C57BL/6 mice aged 6–8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry.
Results:
Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na+/H+ exchanger, Cl–/HCO3 –, and a water channel) and protein expression (butyrate transporter, Na+/H+ exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals.
Conclusion:
Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.
Researcher(s):
Korpela K et al.
Research Unit(s):
Department of Bacteriology and Immunology, Immunobiology Research Programme, Faculty of Medicine, University of Helsinki, Finland
Research Department, Social Insurance Institution, Turku, Finland.
R&D, Valio Ltd, Helsinki, Finland
Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands.
Title of research:
Lactobacillus rhamnosus GG intake modifies preschool children’s intestinal microbiota, alleviates penicillin-associated changes, and reduces antibiotic use.
Scientific/Medical Publication:
PLoS ONE 11(4):e0154012 doi:10.1371/journal.pone.0154012
Reference:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154012
Abstract/Summary:
Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.
Researcher(s):
Vanderhoof JA et al.
Research Unit(s):
Department of Pediatrics, University of Nebraska, Omaha, USA
Black Hills Pediatrics, Children’s Hospital, Rapid City, South Dakota, , USA
Departments of Pediatrics and Psychology, Creighton University, Omaha, Nebraska, USA
Title of research:
Lactobacillus GG in the prevention of antibiotic-associated diarrhoea in children.
Scientific/Medical Publication:
J Pediatr 1999;135:564-568
Reference:
http://www.jpeds.com/article/S0022-3476(99)70053-3/abstract
Abstract/Summary:
Objective:
The objective of this study was to determine the efficacy of Lactobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the incidence of antibiotic-associated diarrhea when coadministered with an oral antibiotic in children with acute infectious disorders.
Study design:
Two hundred two children between 6 months and 10 years of age were enrolled; 188 completed all phases of the protocol. LGG, 1 × 1010 – 2 × 1010 colony forming units per day, or comparable placebo was administered in a double-blind randomized trial to children receiving oral antibiotic therapy in an outpatient setting. The primary caregiver was questioned every 3 days regarding the incidence of gastrointestinal symptoms, predominantly stool frequency and consistency, through telephone contact by blinded investigators.
Results:
Twenty-five placebo-treated but only 7 LGG-treated patients had diarrhea as defined by liquid stools numbering 2 or greater per day. Lactobacillus GG overall significantly reduced stool frequency and increased stool consistency during antibiotic therapy by the tenth day compared with the placebo group. Conclusion: Lactobacillus GG reduces the incidence of antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections.
Researcher(s):
Szajewska H et al.
Research Unit(s):
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Poland.
Title of research:
Probiotics in the prevention of antibiotic-associated diarrhea in children: A meta-analysis of randomized controlled trials.
Scientific/Medical Publication:
J Pediatr 2006;149:367-372
Reference:
http://www.jpeds.com/article/S0022-3476(06)00383-0/abstract
Abstract/Summary:
Objective:
To systematically evaluate the effectiveness of probiotics in preventing antibiotic-associated diarrhea (AAD) in children.
Study design:
The following electronic databases up to December 2005, in any language, were searched for studies relevant to AAD and probiotics: MEDLINE, EMBASE, and The Cochrane Library. Only randomized controlled trials (RCT) were considered for study inclusion.
Results:
Six placebo-controlled, RCTs (766 children) were included. Treatment with probiotics compared with placebo reduced the risk of AAD from 28.5% to 11.9% (relative risk, RR, 0.44, 95% CI 0.25 to 0.77, random effect model). Preplanned subgroup analysis showed that reduction of the risk of AAD was associated with the use of Lactobacillus GG (2 RCTs, 307 participants, RR 0.3, 95% CI 0.15 to 0.6), S. boulardii (1 RCT, 246 participants, RR 0.2, 95% CI 0.07-0.6), or B. lactis & Str. thermophilus (1 RCT, 157 participants, RR 0.5, 95% CI 0.3 to 0.95).
Conclusions:
Probiotics reduce the risk of AAD in children. For every 7 patients that would develop diarrhea while being treated with antibiotics, one fewer will develop AAD if also receiving probiotics.
Researcher(s):
Myllyluoma E et al.
Research Unit(s):
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
Foundation for Nutrition Research, Helsinki, Finland
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
Helsinki University Central Hospital Laboratory, Helsinki, Finland
Valio Ltd, Research Centre, Helsinki, Finland
Title of research:
Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy – a placebo-controlled, double-blind randomized pilot study.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2005;21:1263-1272
Reference:
Abstract/Summary:
Background :
H. pylori is the major cause of chronic gastritis, and a risk factor for peptic ulcer and gastric cancer.
Aim :
To investigate the effect of probiotic supplementation on the tolerance and efficacy of H. pylori eradication treatment in a randomized, double-blind, placebo-controlled trial.
Methods :
A total of 338 volunteers were screened for H. pylori infection. The eligibility criteria were met by 47 subjects whose H. pylori infection was verified at the outset and re-evaluated after the treatment by the 13C-urea breath test and by enzyme immunoassay serology. The subjects were randomized to receive probiotic therapy (Lactobacillus rhamnosus GG, L. rhamnosusLC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS) or a placebo during H. pylori eradication and for 3 weeks following the treatment, and recorded their daily symptoms in a standardized diary.
Results :
When the frequencies of new or aggravated symptoms were evaluated, no significant differences were found between the two groups for individual symptoms. However, the probiotic group showed less treatment-related symptoms as measured by the total symptom score change (P = 0.038) throughout the H. pylori eradication therapy in contrast to the placebo group. The H. pylori eradication rate was non-significantly higher in the group receiving probiotic therapy (91% vs. 79%, P = 0.42). In this group the recovery of probiotic bacteria in the faeces increased significantly (P < 0.001).
Conclusions :
In this pilot study, probiotic supplementation did not diminish significantly the frequency of new or aggravated symptoms during H. pylori eradication. However, our data suggest an improved tolerance to the eradication treatment when total symptom severity was taken into account. Furthermore, the results show that probiotic bacteria are able to survive in the gastrointestinal tract despite the intensive antimicrobial therapy.
Researcher(s):
Johnston BC et al.
Research Unit(s):
McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton, Ontario, Canada
Bastyr University, Seattle, WA, USA
Norwegian Knowledge Centre for the Health Services, Oslo, Norway
Title of research:
Probiotics for the prevention of pediatric antibiotic-associated diarrhea.
Scientific/Medical Publication:
Cochrane Database Syst Rev 2011;11:CD004827
Reference:
Abstract/Summary:
Antibiotic-associated diarrhea (AAD) occurs when antibiotics disturb the natural balance of "good" and "bad" bacteria in the intestinal tract causing harmful bacteria to multiply beyond their normal numbers. The symptoms of AAD include frequent watery bowel movements and crampy abdominal pain. Probiotics are found in dietary supplements or yogurts and contain potentially beneficial bacteria or yeast. Probiotics may restore the natural balance of bacteria in the intestinal tract. Sixteen studies were reviewed and provide the best available evidence. The studies tested 3432 children (2 weeks to 17 years of age) who were receiving probiotics co-administered with antibiotics to prevent AAD. The participants received probiotics (Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination), placebo (pills not including probiotics), other treatments thought to prevent AAD (i.e. diosmectite or infant formula) or no treatment. The studies were short-term, ranging in length from 10 days to 3 months. Analyses showed that probiotics may be effective for preventing AAD. Probiotics were generally well tolerated, and minor side effects occurred infrequently, with no significant difference between probiotic and control groups. Side effects reported in the studies include rash, nausea, gas, flatulence, vomiting, increased phlegm, chest pain, constipation, taste disturbance, and low appetite. The current data suggest that Lactobacillus rhamnosus and Saccharomyces boulardii at a high dosage of 5 to 40 billion CFU/day may prevent the onset of ADD, with no serious side effects documented in otherwise healthy children. This benefit for high dose probiotics needs to be confirmed by a large well designed randomized study. No conclusions about the effectiveness and safety of other probiotic agents for pediatric AAD can be drawn. More refined studies are also needed that evaluate strain specific probiotics and report both the effectiveness (e.g. incidence and duration of diarrhea) and safety of probiotics.
Researcher(s):
D’Souza AL et al.
Research Unit(s):
Care of the Elderly Section, Faculty of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK
Title of research:
Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis.
Scientific/Medical Publication:
BMJ 2002;324:1361-1366
Reference:
http://www.bmj.com/content/324/7350/1361
Abstract/Summary:
Objective:
To evaluate efficacy of probiotics in prevention and treatment of diarrhoea associated with the use of antibiotics.
Design:
Meta-analysis; outcome data (proportion of patients not getting diarrhoea) were analysed, pooled, and compared to determine odds ratios in treated and control groups.
Identification:
Studies identified by searching Medline between 1966 and 2000 and the Cochrane Library.Studies reviewed Nine randomised, double blind, placebo controlled trials of probiotics.
Results:
Two of the nine studies investigated the effects of probiotics in children. Four trials used a yeast (Saccharomyces boulardii), four used lactobacilli, and one used a strain of enterococcus that produced lactic acid. Three trials used a combination of probiotic strains of bacteria. In all nine trials, the probiotics were given in combination with antibiotics and the control groups received placebo and antibiotics. The odds ratio in favour of active treatment over placebo in preventing diarrhoea associated with antibiotics was 0.39 (95% confidence interval 0.25 to 0.62; P<0.001) for the yeast and 0.34 (0.19 to 0.61; P<0.01 for lactobacilli. The combined odds ratio was 0.37 (0.26 to 0.53; P<0.001) in favour of active treatment over placebo.
Conclusions:
The meta-analysis suggests that probiotics can be used to prevent antibiotic associated diarrhoea and that S boulardii and lactobacilli have the potential to be used in this situation. The efficacy of probiotics in treating antibiotic associated diarrhoea remains to be proved. A further large trial in which probiotics are used as preventive agents should look at the costs of and need for routine use of these agents.
Researcher(s):
Luoto R et al.
Research Unit(s):
Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
Department of Virology, University of Turku, Turku, Finland
Functional Foods Forum, University of Turku, Turku, Finland
Title of research:
Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: A randomized, placebo-controlled trial.
Scientific/Medical Publication:
J. Allergy Clin Immunol 2014;133:405-13
Reference:
http://www.jacionline.org/article/S0091-6749(13)01307-9/abstract
Abstract/Summary:
Background：
Simple and safe strategies for the prevention of viral respiratory tract infections (RTIs) are needed.
Objective：
We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants.
Methods：
In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no. NCT00167700), 94 preterm infants (gestational age, ≥32 + 0 and ≤36 + 6 weeks; birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome was the incidence of clinically defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing. Secondary outcomes were the severity and duration of RTIs.
Results：
A significantly lower incidence of RTIs was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12-0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared with those receiving placebo. Also, the incidence of rhinovirus-induced episodes, which comprised 80% of all RTI episodes, was found to be significantly lower in the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49; 95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No differences emerged among the study groups in rhinovirus RNA load during infections, duration of rhinovirus RNA shedding, duration or severity of rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants.
Conclusions：
Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections.
Researcher(s):
Hojsak I et al.
Research Unit(s):
Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, Zagreb, Croatia
Department for Otorinolaringology, General Hospital Dr. Ivo Pedišić, J.J. Strossmayera 59, Sisak, Croatia
2nd Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
Title of research:
Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: A randomised, double-blind, placebo-controlled trial.
Scientific/Medical Publication:
Clin Nutr 2010;29(3):312-316.
Reference:
http://www.clinicalnutritionjournal.com/article/S0261-5614(09)00203-9/abstract
Abstract/Summary:
Background & aims：
The aim of our study was to investigate the role of Lactobacillus GG (LGG) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers.
Methods：
We conducted a randomized, double-blind, placebo-controlled trial in 281 children who attend day care centers. They were randomly allocated to receive LGG at a dose of 109 colony-forming units in 100 ml of a fermented milk product (LGG group, n=139) or placebo that was the same post-pasteurized fermented milk product without LGG (placebo group, n=142) during the 3-month intervention period.
Results：
Compared to the placebo group, children in the LGG group had a significantly reduced risk of upper respiratory tract infections (RR 0.66, 95% CI 0.52 to 0.82, NNT 5, 95% CI 4 to 10), a reduced risk of respiratory tract infections lasting longer than 3 days (RR 0.57, 95% CI 0.41 to 0.78, NNT 5, 95% CI 4 to 11), and a significantly lower number of days with respiratory symptoms (p<0.001). There was no risk reduction in regard to lower respiratory tract infections (RR 0.82, 95% CI 0.24 to 2.76). Compared with the placebo group, children in the LGG group had no significant reduction in the risk of gastrointestinal infections (RR 0.63, 95% CI 0.38 to 1.06), vomiting episodes (RR 0.60, 95% CI 0.29 to 1.24), and diarrheal episodes (RR 0.63, 95% CI 0.35 to 1.11) as well as no reduction in the number of days with gastrointestinal symptoms (p=0.063).
Conclusion：
LGG administration can be recommended as a valid measure for decreasing the risk of upper respiratory tract infections in children attending day care centers.
Researcher(s):
Hojsak I et al.
Research Unit(s):
Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, Zagreb, Croatia
2nd Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland
Department for Environmental and Occupational Health, “Andrija Štampar” School of Public Health, Rockefellerova 4, Zagreb, Croatia
Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Kispaticeva 12, Zagreb, Croatia
Title of research:
Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections.
Scientific/Medical Publication:
Pediatrics 2010;125(5):e1171-1177
Reference:
http://pediatrics.aappublications.org/content/125/5/e1171.long
Abstract/Summary:
Objective:
The incidence of nosocomial infections, predominantly gastrointestinal and respiratory, in children in developed countries is high, ranging from 5% to 44%. There is no effective strategy for preventing these infections. The objective of our study was to investigate the role of LactobacillusGG (LGG) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital.
Methods:
We conducted a randomized, double-blind, placebo-controlled trial of 742 hospitalized children. They were randomly allocated to receive for their hospitalization LGG at a dose of 109 colony-forming units in 100 mL of a fermented milk product (LGG group, n = 376) or placebo that was the same postpasteurized fermented milk product without LGG (placebo group, n = 366).
Results:
In the LGG group, compared with the placebo group, we found a significantly reduced risk for gastrointestinal infections (relative risk [RR]: 0.40 [95% confidence interval (CI): 0.25–0.70]; number needed to treat: 15 [95% CI: 9–34)], respiratory tract infections (RR: 0.38 [95% CI: 0.18–0.85]; number needed to treat: 30 [95% CI: 16–159]), vomiting episodes (RR: 0.5 [95% CI: 0.3–0.9]), diarrheal episodes (RR: 0.24 [95% CI: 0.10–0.50]), episodes of gastrointestinal infections that lasted >2 days (RR: 0.40 [95% CI: 0.25–0.70]), and episodes of respiratory tract infections that lasted >3 days (RR: 0.4 [95% CI: 0.2–0.9]). Groups did not differ in hospitalization duration (P = .1).
Conclusions:
LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities.
Researcher(s):
Lui S et al.
Research Unit(s):
From
the Department of Public Health Microbiology, Department of Public
Health Laboratory Technology, West China School of Public Health,
Sichuan University, China
Title of research:
Lactobacillus
rhamnosus GG Supplementation for Preventing Respiratory Infections in
Children: A Meta-analysis of Randomized, Placebo-controlled Trials.
Scientific/Medical Publication:
Indian Pediatr 2013;50(4):377-81
Reference:
http://www.indianpediatrics.net/apr2013/377.pdf
Abstract/Summary:
Objective:
To
systematically review the effectiveness of administering Lactobacillus
rhamnosus GG (LGG) for preventing respiratory infections in children.
Design:
Systematic Review and Meta-analysis.
Data sources:
Electronic databases and trial registries.
Results:
Four
RCTs involving 1805 participants met the inclusion criteria. Compared
with placebo, LGG administration was associated with a reduced incidence
of acute otitis media (four RCTs, n=1805, RR 0.76, 95% CI 0.64-0.91,
fixed effects model, NNT 17, 95% CI 11-46), a reduced risk of upper
respiratory infections (one RCT, n=281, RR 0.62, 95% CI 0.50-0.78, NNT
4, 95% CI 3-8) and antibiotic treatments (four RCTs, n=1805, RR 0.80,
95% CI 0.71-0.91, fixed effects model). There was no significant
difference between the LGG and the control groups in the risk of overall
respiratory infections and the incidence of lower respiratory
infections. However, subgroup analysis of two studies on children older
than 1 year showed significant reduction in the risk of overall
respiratory infections (two RCTs, n=794, RR 0.73, 95% CI 0.57-0.92,
random effects model, NNT 8, 95% CI 5-14). Adverse effects were similar
in both groups. No serious adverse events were reported.
Conclusion:
The
administration of Lactobacillus rhamnosus GG compared with placebo has
the potential to reduce the incidence of acute otitis media, the upper
respiratory infections and antibiotic use in children.
Researcher(s):
Morrow LE et al.
Research Unit(s):
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Creighton University School of Medicine, Omaha, Nebraska, USA
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA
Department of Allergy and Immunology, Creighton University School of Medicine, Omaha, Nebraska,USA
Title of research:
Probiotic prophylaxis of ventilator-associated pneumonia. A blinded, randomized controlled trial.
Scientific/Medical Publication:
Am J Respir Crit Care Med 2010; 182:1058-1064
Reference:
http://europepmc.org/articles/PMC2970846;jsessionid=KgbJBCETw6lzgKoTiJMP.26
Abstract/Summary:
Rationale:
Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections.
Objectives:
To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP).
Methods:
We performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care.
Measurements and Main Results:
Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile–associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile–associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified.
Conclusions:
These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population.
Researcher(s):
Wong S-S et al.
Research Unit(s):
Pneumococcal Research, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
Allergy and Immune Disorders, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
London School of Hygiene and Tropical Medicine, London, UK
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
Allergy and Immunology, Royal Children’s Hospital, Parkville, VIC, Australia
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia
Title of research:
Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in vitro by the probiotic Lactobacillus rhamnosus GG.
Scientific/Medical Publication:
BMC Research Notes 2013;6:135
Reference:
http://www.biomedcentral.com/1756-0500/6/135
Abstract/Summary:
Background:
Colonization of the nasopharynx by Streptococcus pneumoniae is considered a prerequisite for pneumococcal infections such as pneumonia and otitis media. Probiotic bacteria can influence disease outcomes through various mechanisms, including inhibition of pathogen colonization. Here, we examine the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on S. pneumoniae colonization of human epithelial cells using an in vitro model. We investigated the effects of LGG administered before, at the same time as, or after the addition of S. pneumoniae on the adherence of four pneumococcal isolates.
Results:
LGG significantly inhibited the adherence of all the pneumococcal isolates tested. The magnitude of inhibition varied with LGG dose, time of administration, and the pneumococcal isolate used. Inhibition was most effective when a higher dose of LGG was administered prior to establishment of pneumococcal colonization. Mechanistic studies showed that LGG binds to epithelial cells but does not affect pneumococcal growth or viability. Administration of LGG did not lead to any significant changes in host cytokine responses.
Conclusions:
These findings demonstrate that LGG can inhibit pneumococcal colonization of human epithelial cells in vitro and suggest that probiotics could be used clinically to prevent the establishment of pneumococcal carriage.
Researcher(s):
Kawase M et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Kanagawa, Japan
Title of research:
Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection.
Scientific/Medical Publication:
Lett Appl Microbiol 2010;51(1):6-10
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1472-765X.2010.02849.x/abstract
Abstract/Summary:
Aims:
Our study was conducted to evaluate the potent protective effects of oral administration of probiotic Lactobacillus strains against influenza virus (Flu) infection in a mouse model.
Method and Results:
Lyophilized Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri TMC0356 (TMC0356) were orally administered to BALB/c mice for 19 days. The test mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and any changes in clinical symptoms were monitored. After 6 days of infection, the mice were killed and pulmonary virus titres were determined. The clinical symptom scores of mice administered oral LGG and TMC0356 were significantly ameliorated, compared to those of the control mice (P < 0·01). The pulmonary virus titres of the mice fed LGG and TMC0356 were also significantly decreased compared to those of control mice (P < 0·05).
Conclusions:
These results indicate that oral administration of lactobacilli, such as LGG and TMC0356, might protect a host animal against Flu infection.
Researcher(s):
Harata G et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd.,Yokohama, Kanagawa, Japan
Department of Sciences of Functional Foods, Graduate School of Agriculture, Shinshu University, Minami-minowa, Kami-ina, Nagano, Japan
Title of research:
Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.
Scientific/Medical Publication:
Lett Appl Microbiol 2010;50:597-602
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1472-765X.2010.02844.x/abstract
Abstract/Summary:
Aims:
To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model.
Methods and Results:
After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0·05). The YAC-1 cell-killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0·01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)-1β, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)-1 (P < 0·01).
Conclusions:
These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell-mediated immune responses following up-regulation of lung natural killer (NK) cell activation.
Significance and Impact of Study:
We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.
Researcher(s):
Princivalli MS et al.
Research Unit(s):
Institute of Microbiology and Biomedical Sciences, Polytechnic University of Marche, Medical School, Ancona, Italy
Title of research:
Lactobacillus rhamnosus GG inhibits invasion of cultured human respiratory cells by prtF1-positive macrolide-resistant group A streptococci.
Scientific/Medical Publication:
Letts Appl Microbiol 2009;48(3):368-372
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1472-765X.2008.02540.x/abstract
Abstract/Summary:
Aims:
This study was designed to determine whether the probiotic strain Lactobacillus GG, which is extensively used in the treatment and prevention of intestinal disorders, is able to inhibit invasion of cultured human respiratory cells by macrolide-resistant group A streptococci (GAS) carrying the prtF1 gene, which encodes the fibronectin (Fn)-binding invasin F1.
Methods and Results:
Eight prtF1-positive erythromycin-resistant GAS strains were used to infect A549 monolayers in competition and displacement assays with Lactobacillus GG. Live (L-LGG) and heat-killed (HK-LGG) lactobacilli and their spent culture supernatant (SCS) significantly reduced (P < 0·001) GAS invasion efficiency in both assays. No antibacterial activity of Lactobacillus GG against GAS was detected. Both L-LGG and HK-LGG and all prtF1-positive GAS induced a strong agglutination reaction using Fn-coated particles.
Conclusions:
Lactobacillus GG exerts an antagonistic action against GAS by inhibiting cell invasion. Competitive binding of Lactobacillus GG and GAS to Fn might be involved in the inhibition process.
Significance and Impact of the Study:
The finding that Lactobacillus GG can prevent in vitro invasion of respiratory cells by GAS suggests new applications for this probiotic strain and warrants further studies of its capacity to prevent GAS throat infections.
Researcher(s):
Gluck U et al.
Research Unit(s):
Suva, Swiss National Accident Insurance Institute, Division of Occupational Medicine, Lucerne, Switzerland (UG), and the lnstitute of Pathology and Environmental Medicine, Kantonsspital Luzern, Lucerne, Switzerland
Title of research:
Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae and beta-hemolytic streptococci).
Scientific/Medical Publication:
Am J Clin Nutr 2003;77(2):517-520
Reference:
http://ajcn.nutrition.org/content/77/2/517.long
Abstract/Summary:
Background:
As a bacterial reservoir, the nose may harbor potentially pathogenic bacteria (PPB: Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, and Haemophilus influenzae). In patients carrying PPB, antiseptic regimens could be crucial for infection control after major operations on or injuries of the head, nasal sinuses, or lungs. Such regimens may also be important for diabetic patients and persons receiving hemodialysis, in intensive care units, or with impaired immunity due to various other causes.
Objective:
We tested a possible effect of the ingestion of probiotics on the bacterial flora of the nose.
Design:
In an open, prospective trial, 209 volunteers were randomly assigned to consume either a probiotic, fermented milk drink [65 mL with Lactobacillus GG (ATCC 53103), Bifidobacterium sp B420, Lactobacillus acidophilus 145, and Streptococcus thermophilus; n = 108] or standard yogurt (180 g; n = 101) daily for 3 wk. Nasal microbial flora were analyzed on days 1, 21, and 28. The microbial examination was blinded to the source of the samples.
Results:
We found a significant reduction (19%; P < 0.001) in the occurrence of nasal PPB in the group who consumed the probiotic drink but not in the group who consumed yogurt. The effect was mainly on gram-positive bacteria, which decreased significantly (P < 0.05).
Conclusions:
The results indicate that regular intake of probiotics can reduce PPB in the upper respiratory tract. The results also indicate a linkage of the lymphoid tissue between the gut and the upper respiratory tract.
Researcher(s):
Hatakka K et al.
Research Unit(s):
Valio Research and Development, PO Box 30, FIN-00039 Valio, Helsinki, Finland
Hospital for Children and Adolescents, Helsinki University Central Hospital, FIN-00029 Helsinki, Finland
Centre of the Environment, Helsinki City, Helsinginkatu 24, FIN-00530 Helsinki, Finland
STAT-Consulting, Takojankatu 15 B, FIN-33540 Tampere, Finland
Department of Oral and Dental Diseases, Helsinki University Hospital, PO Box 263, FIN-00029 HUS, Helsinki, Finland
Helsinki City Health Department, Kytösuontie 9, FIN-00030 Helsinki, Finland
Foundation for Nutrition Research, PO Box 30, FIN-00039 Helsinki, Finland
Title of research:
Effect on long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial.
Scientific/Medical Publication:
BMJ 2001;322:1327-1329
Reference:
http://www.bmj.com/content/322/7298/1327?view=long&pmid=11387176
Abstract/Summary:
Objective:
To examine whether long term consumption of a probiotic milk could reduce gastrointestinal and respiratory infections in children in day care centres.
Design:
Randomised, double blind, placebo controlled study over seven months.
Setting:
18 day care centres in Helsinki, Finland.
Participants:
571 healthy children aged 1-6 years: 282 (mean (SD) age 4.6 (1.5) years) in the intervention group and 289 (mean (SD) age 4.4 (1.5) years) in the control group.
Intervention:
Milk with or without Lactobacillus GG. Average daily consumption of milk in both groups was 260 ml.
Main outcome measures:
Number of days with respiratory and gastrointestinal symptoms, absences from day care because of illness, respiratory tract infections diagnosed by a doctor, and course of antibiotics.
Results:
Children in the Lactobacillus group had fewer days of absence from day care because of illness (4.9 (95% confidence interval 4.4 to 5.5) v 5.8 (5.3 to 6.4) days, 16% difference, P=0.03; age adjusted 5.1 (4.6 to 5.6) v 5.7 (5.2 to 6.3) days, 11% difference, P=0.09). There was also a relative reduction of 17% in the number of children suffering from respiratory infections with complications and lower respiratory tract infections (unadjusted absolute % reduction −8.6 (−17.2 to −0.1), P=0.05; age adjusted odds ratio 0.75 (0.52 to 1.09), P=0.13) and a 19% relative reduction in antibiotic treatments for respiratory infection (unadjusted absolute % reduction −9.6 (−18.2 to −1.0), P=0.03; adjusted odds ratio 0.72 (0.50 to 1.03), P=0.08) in the Lactobacillus group.
Conclusions:
Lactobacillus GG may reduce respiratory infections and their severity among children in day care. The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction.
Researcher(s):
Hatakka K et al.
Research Unit(s):
Valio Ltd, R&D, PO Box 30, FIN-00039 Helsinki, Finland.
Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Finland
Institute of Dentistry, University of Helsinki, Finland
Department of Bacteriology and Immunology, University of Helsinki, Finland
STAT-Consulting, Tampere, Finland
Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Finland
Foundation for Nutrition Research, Helsinki, Finland
Title of research:
Probiotics reduce the prevalence of oral Candida in the elderly – a randomized controlled trial.
Scientific/Medical Publication:
J Dent Res 2007;86(2):125-130
Reference:
http://jdr.sagepub.com/content/86/2/125.short
Abstract/Summary:
Overgrowth of oral yeast is a common problem among the elderly. Probiotic bacteria are known to inhibit the growth of pathogenic microbes. We tested the hypothesis that cheese containing probiotic bacteria can reduce the prevalence of oral Candida. During this 16-week, randomized, double-blind, placebo-controlled study, 276 elderly people consumed daily 50 g of either probiotic (n = 136) or control cheese (n = 140). The primary outcome measure was the prevalence of a high salivary yeast count (>or= 10(4) cfu/mL) analyzed by the Dentocult method. The prevalence decreased in the probiotic group from 30% to 21% (32% reduction), and increased in the control group from 28% to 34%. Probiotic intervention reduced the risk of high yeast counts by 75% (OR = 0.25, 95%CI 0.10-0.65, p = 0.004), and the risk of hyposalivation by 56% (OR = 0.44, 95%CI 0.19-1.01, p = 0.05). Thus, probiotic bacteria can be effective in controlling oral Candida and hyposalivation in the elderly.
Researcher(s):
Kukkonen K et al.
Research Unit(s):
Department of Pediatrics, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Department of Pediatrics, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
STAT Consulting, Tampere, Finland
Valio Research and Development, Helsinki, Finland
Title of research:
Long-term safety and impact on infection rates on postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial.
Scientific/Medical Publication:
Pediatrics 2008;122:8-12
Reference:
http://pediatrics.aappublications.org/content/122/1/8.long
Abstract/Summary:
Objective：
Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants.
Methods:
Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point.
Results:
Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections).
Conclusion:
Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.
Researcher(s):
Rautava S et al.
Research Unit(s):
Department of Paediatrics, University of Turku, Turku, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Title of research:
Specific probiotics in reducing the risk of acute infections in infancy - a randomised, double-blind. placebo-controlled study.
Scientific/Medical Publication:
Br J Nutr 2009;101(11):1722-1726
Reference:
http://agris.fao.org/agris-search/search.do?recordID=US201301646485
Abstract/Summary:
A randomised, double-blind, placebo-controlled study was conducted to determine whether probiotics might be effective in reducing the risk of infections in infancy. Infants requiring formula before the age of 2 months were recruited from community well-baby clinics. Infant formula supplemented with the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 or placebo was administered daily until the age of 12 months. Incidence of early infections (before the age of 7 months) and incidence of recurrent (three or more) infections during the first year of life were recorded as the main outcome measures of the study. During the first 7 months of life, seven out of thirty-two (22 %) infants receiving probiotics and twenty out of forty (50 %) infants receiving placebo experienced acute otitis media (risk ratio (RR) 0·44 (95 % CI 0·21, 0·90); P = 0·014) and antibiotics were prescribed for ten out of thirty-two (31 %) infants receiving probiotics and twenty-four out of forty (60 %) infants receiving placebo (RR 0·52 (95 % CI 0·29, 0·92); P = 0·015). During the first year of life, nine out of thirty-two (28 %) infants receiving probiotics and twenty-two out of forty (55 %) infants receiving placebo encountered recurrent respiratory infections (RR 0·51 (95 % CI 0·27, 0·95); P = 0·022).
Researcher(s):
Davidson LE et al.
Research Unit(s):
Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, MA, USA
Title of research:
Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial.
Scientific/Medical Publication:
Eur J Clin Nutr 2011;65(4):501-7
Reference:
http://www.nature.com/ejcn/journal/v65/n4/full/ejcn2010289a.html
Abstract/Summary:
Background/Objectives:
Live-attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration.
Subjects/Methods:
We conducted a randomized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007–2008 influenza season. All subjects received LAIV and then were randomized to LGG or placebo, twice daily for 28 days. Hemagglutinin inhibition titers were assessed at baseline, at day 28 and at day 56 to determine the rates of seroconversion. Subjects were assessed for adverse events throughout the study period.
Results:
A total of 39 subjects completed the per-protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% confidence interval 1.04–3.22, P=0.048).
Conclusion:
Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects, target mucosal immune responses or focus on groups known to have poor response to influenza vaccines.
Researcher(s):
de Vrese M et al.
Research Unit(s):
Federal Research Centre of Nutrition and Food, Institute of Physiology and Biochemistry of Nutrition, Hermann-Weigmann-Straße 1, Kiel, Germany
Institute for Medical Microbiology and Virology, Christian-Albrechts-University, Brunswiker Str. 4, Kiel, Germany
National Institute of Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands
Title of research:
Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination.
Scientific/Medical Publication:
Eur J Nutr 2005;44(7):406-413
Reference:
http://europepmc.org/abstract/MED/15578195
Abstract/Summary:
Background:
Orally ingested probiotic bacteria may modulate the immune response and increase antibody titers against enteric infections by bacteria or viruses. Even though positive effects of probiotics on respiratory tract infections have been reported, overall only few studies have examined effects on virus infections concerning organs other than the gastrointestinal tract.
Aim of the study:
It was the aim of the study to investigate whether and how probiotics affect the immune response to a standardized enterovirus challenge (polio) and infections not limited to the gastrointestinal tract in healthy adults.
Methods:
In a randomized, controlled and double-blind study 64 volunteers consumed for 5 weeks chemically acidified clotted milk without bacteria or with 10(10)/serving (Lactobacillus rhamnosus ) GG or Lactobacillus acidophilus CRL431 added. In the second week subjects were vaccinated orally against polio 1, 2 and 3. Polio virus neutralizing serum activity, the primary parameter, was determined by the standard neutralization test (WHO) before and three times after vaccination. Polio-specific IgA, IgG and IgM were detected by ELISAs.
Results:
Probiotics increased poliovirus neutralizing antibody titers (NT) and affected the formation of poliovirus-specific IgA and IgG in serum. The maximum increase after immunization was about 2, 2.2, or 4-fold higher, respectively, for NT, IgG or, IgA, in volunteers consuming probiotics instead of placebo. No consistent difference was noted between bacterial strains.
Conclusions:
Probiotics induce an immunologic response that may provide enhanced systemic protection of cells from virus infections by increasing production of virus neutralizing antibodies.
Researcher(s):
Kukkonen K et al.
Research Unit(s):
Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
STAT-consulting, Tampere, Finland
Title of research:
Effect of probiotics on vaccine antibody responses in infancy - a randomized placebo-controlled double-blind trial.
Scientific/Medical Publication:
Pediatr Allergy Immunol 2006;17(6):416-421
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-3038.2006.00420.x/abstract
Abstract/Summary:
Probiotics are immunomodulatory and may thus affect vaccine antibody responses. With the accumulating evidence of their health-promoting effects, probiotics are increasingly administered in allergy-prone infants. Therefore, we studied the effect of probiotics on antibody responses to diphtheria, tetanus and Haemophilus influenzae type b (Hib) vaccines in 6-month-old infants participating in a randomized placebo-controlled double-blind allergy-prevention trial. Mothers of unborn children at increased risk for atopy used a combination of four probiotic strains, or a placebo, for 4 wk before delivery. During 6 months from birth, their infants received the same probiotics and galacto-oligosaccharides, or a placebo. The infants were immunized with a DTwP (diphtheria, tetanus and whole cell pertussis) at ages 3, 4, and 5 months, and with a Hib polysaccharide conjugate at 4 months. Serum diphtheria, tetanus, and Hib IgG antibodies were measured at 6 months. In the probiotic group, protective Hib antibody concentrations (≥1 μg/ml) occurred more frequently, 16 of 32 (50%) vs. six of 29 (21%) (p = 0.020), and the geometric mean (inter-quartile range) Hib IgG concentration tended to be higher 0.75 (0.15–2.71) μg/ml than in the placebo group 0.40 (0.15–0.92) μg/ml (p = 0.064). In these respective groups, diphtheria, 0.38 (0.14–0.78) vs. 0.47 (0.19–1.40) IU/ml (p = 0.449), and tetanus, 1.01(0.47–1.49) vs. 0.81 (0.56–1.39) IU/ml (p = 0.310), IgG titers were comparable. In conclusion, in allergy-prone infants probiotics seem not to impair antibody responses to diphtheria, tetanus, or Hib, but may improve response to Hib immunization.
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Clinical Medicine, University of Tampere, Tampere, Finland
Department of Biomedical Sciences, University of Tampere, Tampere, Finland
Title of research:
Improved immunogenicity of oral DxRRV reassortant rotavirus vaccine by Lactobacillus casei GG.
Scientific/Medical Publication:
Vaccine 1995;13(3):310-312
Reference:
http://www.sciencedirect.com/science/article/pii/0264410X95933195
Abstract/Summary:
In a search for new strategies to improve oral vaccination, the effect of orally administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV rhesus-human reassortant live oral rotavirus vaccine was tested in 2-5-month-old infants. Infants who received LGG showed an increased response with regard to rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on day 8 after vaccination. In infants receiving LGG or placebo, respectively, a rotavirus IgM seroconversion was detected in 26/27 (96%), versus 23/27 (85%) cases (p = 0.15) and rotavirus IgA seroconversion was detected in 26/28 (93%) versus 20/27 (74%) cases (p = 0.05). These findings suggest that LGG has an immunostimulating effect on oral rotavirus vaccination. The clinical significance of LGG-enhanced immune responses to oral vaccines should be further evaluated.
Researcher(s):
Manzoni P et al.
Research Unit(s):
Neonatology and Hospital Neonatal Intensive Care Unit, Azienda Ospedaliera Regina Margherita-S. Anna, Turin, Italy
Department of Clinical Pathology and Microbiology, Azienda Ospedaliera Regina Margherita-S. Anna, Turin, Italy
Department of Pediatric Sciences, University of Torino, Turin, Italy
Title of research:
Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.
Scientific/Medical Publication:
ClD 2006;42:1735-42
Reference:
http://www.jstor.org/discover/10.2307/4484834?uid=3738672&uid=2&uid=4&sid=21103967
Abstract/Summary:
Background:
Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6times10⁹ cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e.,<1500-g) neonates during their stay in a neonatal intensive care unit. Methods. Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract. Results. The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P = .01). The numbers of fungal isolates obtained from each neonate (P = .005) and from each colonized patient (P = .005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded. Conclusions. Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.
Researcher(s):
Manzoni P et al.
Research Unit(s):
Neonatal Intensive Care Unit (NICU), S. Anna Hospital, Torino, Italy.
NICU, Ospedali Riuniti, Foggia, Italy.
NICU, University of Modena, Modena, Italy
NICU, IRCCS Mangiagalli Hospital, Milano, Italy
NICU, Azienda Ospedaliera Universitaria Policlinico, Catania, Italy
NICU, Ospedale Regionale, Bolzano, Italy
NICU, Policlinico Umberto I, Rome, Italy
NICU, IRCCS San Matteo, Pavia, Italy
NICU, Policlinico University Hospital, Bari, Italy
NICU, Arcispedale S. M. Nuova, Reggio Emilia, Italy
NICU, Ca’ Foncello Hospital, Treviso, Italy
Departments of Biomedical Sciences and Human Oncology, Cancer Epidemiology Unit, University of Torino, Torino
Department of Pediatrics, University of Torino, Torino, Italy.
Title of research:
Bovine lactoferrin supplementation for prevention of late-onset sepsis in very-low-birth.weight neonates: a randomized trial.
Scientific/Medical Publication:
JAMA 2009;302(13):1421-1428
Reference:
http://jama.jamanetwork.com/article.aspx?articleid=184658
Abstract/Summary:
Context:
Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.
Objective:
To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.
Design:
Setting, and Patients Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.
Intervention:
Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 × 109 colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates<1000 g at birth).
Main Outcome Measure:
First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.
Results:
Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.
Conclusion:
Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.
Researcher(s):
Bruzzese E et al.
Research Unit(s):
Department of Pediatrics, University of Naples “Federico II”, Via S. Pansini 5, 80131 Naples, Italy
Institute of Child Health, University College London, London, UK
European Institute of Research in Cystic Fibrosis, Verona, Italy
Title of research:
Effect of Lactobacillus GG supplementation on pulmonary exacerbations in pulmonary exacerbations in patients with cystic fibrosis: A pilot study.
Scientific/Medical Publication:
Clin Nutr 2007;26(3):322-328
Reference:
http://www.clinicalnutritionjournal.com/article/S0261-5614(07)00029-5/abstract
Abstract/Summary:
Background & aims:
Probiotics reduce intestinal inflammation in children with cystic fibrosis (CF). We want to determine the effects of Lactobacillus GG (LGG) on pulmonary exacerbations in CF.
Methods:
A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV1), and modifications of body weight.
Results:
Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5–1.5; p=0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI95% 1.0–1.5; p=0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV1 (3.6%±5.2 vs. 0.9%±5; p=0.02) and body weight (1.5kg±1.8 vs. 0.7kg±1.8; p=0.02).
Conclusions:
LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.
Researcher(s):
Lu R et al.
Research Unit(s):
University of Maryland School of Medicine, Mucosal Biology Research Center, Health Science Baltimore, USA
University of Maryland College Park, USA
Proteomic Core Facility, USA
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD,USA
Title of research:
Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2009;49(1):23-30
Reference:
http://europepmc.org/abstract/MED/19465870
Abstract/Summary:
Objectives:
Diarrheal diseases remain a major human plague that still claim millions of lives every year. Probiotics, including Lactobacillus GG (LGG), are known to have a beneficial effect on diarrheal diseases, but their mechanism of action has not yet been completely established. Therefore, the main objective of this work was to identify and characterize moieties elaborated by LGG that exert antibacterial activity.
Materials and Methods:
Lactobacillus GG conditional media was subjected to liquid chromatography/mass spectrometry. The identified peptides were synthesized by Symphony peptide synthesizer and purified by HPLC using Dynamax reverse-phase C18 column. Using A600 measurement and tested for their antibacterial activity.
Results:
We identified 7 small peptides from LGG cultured media, 2 of which are NPSRQERR and PDENK, retained the antibacterial activity detected with LGG conditional media. The antibacterial activity was exerted against both Gram-negative (Escherichia coli EAEC 042 and Salmonella typhi) and, with less potency, Gram-positive (Staphylococcus aureus) bacteria.
Conclusions:
Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity. NPSRQERR showed the most potent antibacterial effect that was detected both in Gram-negative and Gram-positive microorganisms. These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.
Researcher(s):
Pelto L et al.
Research Unit(s):
Department of Biochemistry and Food Chemistry, University of Turku, Finland
Department of Paediatrics, University of Turku, Finland
Title of research:
Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immmunostimulatory effect in healthy subjects.
Scientific/Medical Publication:
Clin Exp Allergy 1998;28:1474-1479
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2222.1998.00449.x/abstract;jsessionid=
9765DBE3836CCAB01620DD71EDBE9FD8.f03t01
Abstract/Summary:
Background:
Probiotic bacteria can influence immune responses both specifically by stimulating antibody production and nonspecifically by enhancing phagocytosis of pathogens and modifying cytokine production.
Objective:
The authors hypothesized that probiotic bacteria can alleviate hypersensitivity by influencing phagocytes. The modulation of phagocytes may be different in healthy subjects compared with hypersensitive subjects.
Subjects and methods:
In a double-blind, cross-over study, challenges with milk in milk-hypersensitive and healthy adults with or without an intestinal bacterial strain, Lactobacillus GG (ATCC 53103) were performed. The challenge-induced immunoinflammatory response was recorded by measuring the expression of phagocytosis receptors prior to and after the challenge using flow cytometry.
Results:
In milk-hypersensitive subjects, milk challenge increased significantly the expression of CR1, FcγRI and FcαR in neutrophils and CR1, CR3 and FcαR in monocytes. Milk with Lactobacillus GG prevented the increase of the receptor expression. In healthy subjects, milk challenge did not influence receptor expression while milk with Lactobacillus GG increased significantly the expression of CR1, CR3, FcγRIII and FcαR in neutrophils.
Conclusion:
Probiotic bacteria appear to modulate the nonspecific immune response differently in healthy and hypersensitive subjects. This is seen as an immunostimulatory effect in healthy subjects, and as a down-regulation of immunoinflammatory response in milk-hypersensitive subjects.
Researcher(s):
Sanchez B et al.
Research Unit(s):
Université de Bordeaux, UMR 5248 CNRS, UBX1-ENITAB, ENITAB, Gradignan Cedex, France
Université de Bordeaux, UMR 5248 CNRS, UBX1-ENITAB, Institut Européen de Chimie et Biologie 2, Pessac, France
Title of research:
Identification of novel proteins secreted by Lactobacillus rhamnosus GG grown in de Mann-Rogosa-Sharpe broth.
Scientific/Medical Publication:
Lett Appl Mocrobiol 2009;48(5):616-622
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1472-765X.2009.02579.x/abstract
Abstract/Summary:
Aims:
To identify novel proteins secreted by the probiotic bacterium Lactobacillus rhamnosus GG after growth in de Mann-Rogosa-Sharpe broth (MRS), a complex medium often used for the culture of Lactobacillus.
Methods and Results:
The proteins secreted by L. rhamnosus GG strain were precipitated using a trichloroacetic acid-based protocol, resolved by SDS-PAGE, and identified by tandem mass spectrometry (MS/MS). Among the proteins secreted by this bacterium, a leukocyte elastase inhibitor, already present in the MRS broth, was identified. Other proteins such as cell wall hydrolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase, and an extracellular transcriptional regulator have been also identified.
Conclusions:
Lactobacillus rhamnosus GG secretes several proteins during its growth in MRS, some of them with assigned functions in the prevention of the molecular mechanisms that lead to damage in the epithelial barrier (cell wall hydrolase) and in adhesion (GAPDH). The rest of the proteins require further genetic analysis in order to establish their precise roles. None of the proteins bound to mucin or fibronectin.
Significance and Impact of the Study:
Some of these secreted proteins could be involved in the probiotic effects exerted by L. rhamnosus GG strain, their identification being the first step towards in depth functional studies.
Researcher(s):
Silva M et al.
Research Unit(s):
Department of Community Health, Tufts University School of Medicine, Boston, MA, USA
Department of Pathology, new England Medical Centre Hospitals, Boston, MA, USA
Title of research:
Antimicrobial substance from a human Lactobacillus strain.
Scientific/Medical Publication:
Antimicrob Agents Chemother 1987;31(8):1231-1233
Reference:
http://aac.asm.org/content/31/8/1231.short
Abstract/Summary:
Lactobacillus sp. strain GG, which was isolated from the feces of a normal person, produced a substance with potent inhibitory activity against a wide range of bacterial species. It inhibited anaerobic bacteria (Clostridium spp., Bacteroides spp., Bifidobacterium spp.), members of the family Enterobacteriaceae, Pseudomonas spp. Staphylococcus spp., and Streptococcus spp., as demonstrated by a microbiological assay; however, it did not inhibit other lactobacilli. The inhibitory activity occurred between pH 3 and 5 and was heat stable. Bactericidal activity against Escherichia coli was demonstrated at a dilution of 1:128. The inhibitory substance was distinct from lactic and acetic acids. It had a low molecular weight (less than 1,000) and was soluble in acetone-water (10:1). Because of these characteristics, the inhibitory material could not be considered a bacteriocin; it most closely resembled a microcin, which has been associated previously with members of the family Enterobacteriaceae.
Researcher(s):
Khailova L. et al.
Research Unit(s):
Division of Infectious Diseases, University of Colorado School of Medicine, and Microbiome Research Consortium, University of Colorado, Aurora, Colorado.
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
Title of research:
Probiotic administration reduces mortality and improves intestinal epithelial homeostasis in experimental sepsis.
Scientific/Medical Publication:
Anaesthesiology 2013;119(1):166-177
Reference:
http://www.pubfacts.com/detail/23571641?PMID=23571641
Abstract/Summary:
Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis.
Cecal ligation and puncture (n=14 per group) or sham laparotomy (n=8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n=14; BL, n=10; or vehicle, n=13; shams, n=3 per group).
Probiotics significantly improved mortality after sepsis (92 vs. 57% mortality for LGG and 92 vs. 50% mortality for BL; P=0.003). Bacteremia was markedly reduced in septic mice treated with either probiotic compared with vehicle treatment (4.39±0.56 vs. 1.07±1.54; P=0.0001 for LGG; vs. 2.70±1.89; P=0.016 for BL; data are expressed as mean±SD). Sepsis in untreated mice increased colonic apoptosis and reduced colonic proliferation. Probiotics significantly reduced markers of colonic apoptosis and returned colonic proliferation to sham levels. Probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals. Our data suggest that involvement of the protein kinase B pathway (via AKT) and down-regulation of Toll-like receptor 2/Toll-like receptor 4 via MyD88 in the colon may play mechanistic roles in the observed probiotic benefits.
Our data demonstrate that probiotic administration at initiation of sepsis can improve survival in pediatric experimental sepsis. The mechanism of this protection involves prevention of systemic bacteremia, perhaps via improved intestinal epithelial homeostasis, and attenuation of the local and systemic inflammatory responses.
Researcher(s):
Kumpu M et al.
Research Unit(s):
Valio Ltd, Helsinki, Finland
Institute of Biomedicine, University of Helsinki, Helsinki, Finland
Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland
Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland
Medcare Foundation, Äänekoski, Finland
Department of Otorhinolaryngology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
Title of research:
The Use of the Probiotic Lactobacillus rhamnosus GG and Viral Findings in the Nasopharynx of Children Attending Day Care.
Scientific/Medical Publication:
J Med Virol; 2013:85:1632-1638
Reference:
http://onlinelibrary.wiley.com/doi/10.1002/jmv.23623/abstract
Abstract/Summary:
Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses in children attending day care. In this substudy of a randomized, double-blinded, placebo-controlled 28-week intervention study, nasopharyngeal swab samples were collected, on visits to a physician due to symptoms of infection, from children receiving control milk (N = 97) and children receiving the same milk supplemented with probiotic Lactobacillus rhamnosus GG (N = 97). The presence of 14 respiratory viruses was assessed by PCR methods, and viral findings were compared with symptom prevalences in the intervention groups. Rhinovirus was identified in 28.6% of 315 swab samples, followed by respiratory syncytial virus (12.4%), parainfluenza virus 1 (12.1%), enterovirus (8.9%), influenza A(H1N1)pdm09 (7.9%), human bocavirus 1 (3.8%), parainfluenza virus 2 (3.2%), adenovirus (2.9%), and influenza A(H3N2) (0.6%). The children in the probiotic group had less days with respiratory symptoms per month than the children in the control group (6.48 [95% CI 6.28–6.68] vs. 7.19 [95% CI 6.98–7.41], P < 0.001). Probiotic intervention did not reduce significantly the occurrence of the examined respiratory viruses, or have an effect on the number of respiratory symptoms observed at the time of a viral finding. Rhinovirus, respiratory syncytial virus, and parainfluenza virus 1 were the most common respiratory viruses in symptomatic children. Children receiving Lactobacillus rhamnosus GG had fewer days with respiratory symptoms than children in the control group, although probiotic intervention was not effective in reducing the amount of viral findings or the respiratory symptoms associated with viral findings.
Researcher(s):
Hao Q et al.
Research Unit(s):
West China Hospital, Sichuan University, Department of Geriatrics, Chengdu, Sichuan, China
West China Hospital, Sichuan University, Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, Chengdu, Sichuan, China
Title of research:
Probiotics for preventing acute upper respiratory tract infections.
Scientific/Medical Publication:
Cochrane Database Syst Rev. 2011 Sep 7;(9):CD006895.
Reference:
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006895.pub2/abstract
Abstract/Summary:
Background:
Probiotics may improve a person's health by regulating their immune function. Some studies show that probiotic strains can prevent respiratory infections. However, no evidence of the benefits of probiotics for acute upper respiratory tract infections (URTIs) and related potential adverse effects has been published.
Objectives:
To assess the effectiveness and safety of probiotics for preventing acute URTIs.
Main results:
We included 14 RCTs, although we could only extract available data to meta-analyse in 10 trials which involved 3451 participants. We found that probiotics were better than placebo when measuring the number of participants experiencing episodes of acute URTI: at least one episode: odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.92; at least three episodes: OR 0.53; 95% CI 0.36 to 0.80; rate ratio of episodes of acute URTI: rate ratio 0.88; 95% CI 0.81 to 0.96; and reduced antibiotic prescription rates for acute URTIs: OR 0.67; 95% CI 0.45 to 0.98. Probiotics and placebo were similar when measuring the mean duration (MD) of an episode of acute URTI: MD -0.29; 95% CI -3.71 to 3.13 and adverse events: OR 0.92; 95% CI 0.37 to 2.28. Side effects of probiotics were minor and gastrointestinal symptoms were the most common. We found that some subgroups had a high level of heterogeneity when conducting pooled analyses.
Authors' conclusions:
Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTIs, the rate ratio of episodes of acute URTI and reducing antibiotic use. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the results have some limitations and there were no data for older people.
Researcher(s):
Guarino A et al.
Research Unit(s):
Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
Schneider Children's Medical Center, Tel-Aviv University, Tel-Aviv, Israel
University Paris 5 and Necker-Enfants-Malades, Paris, France
Medical University of Warsaw, Department of Pediatrics, Warsaw, Poland.
Title of research:
European Society for Paediatric Gastroenterology, Hepatology and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe.
Scientific/Medical Publication:
J Ped Gastroenterol Nutr 2008;46:S81-S184
Reference:
http://www.ncbi.nlm.nih.gov/pubmed/24739189
Abstract/Summary:
Objectives:
These guidelines update and extend evidence-based indications for the management of children with acute gastroenteritis in Europe.
Methods:
The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir Gray system and, in parallel, with the Grading of Recommendations, Assessment, Development and Evaluations system.
Results:
Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypoosmolar solution is the major treatment and should start as soon as possible. Breast-feeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Data suggest that in the hospital setting, in non-breast-fed infants and young children, lactose-free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or racecadotril. Anti-infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an outpatients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates.
Conclusions:
Acute gastroenteritis is best managed using a few simple, well-defined medical interventions.
Researcher(s):
-
Research Unit(s):
College of Paediatrics, Academy of Medicine of Malaysia (AMMCOP)
Malaysian Paediatric Association (MPA)
Title of research:
The management of acute diarrhoea in children. A guide for healthcare professionals. College of Paediatrics
Scientific/Medical Publication:
Academy of Medicine of Malaysia and Malaysia Paediatric Association, 2011.
Reference:
http://www.acadmed.org.my/index.cfm?&menuid=83&parentid=34
Abstract/Summary:
-
Researcher(s):
Kaila M et al.
Research Unit(s):
Department of Clinical Sciences, University of Tampere, Tampere, Finland
Department of Clinical Microbiology, Division of Clinical Immunology, Tampere University Hospital, Tampere, Finland
National Public Health Institute, Turku, Finland
Title of research:
Enhancement of the circulating antibody secreting cell response in human diarrhea by a human lactobacillus strain.
Scientific/Medical Publication:
Pediatr Res 1992;32(2):141-144
Reference:
http://www.nature.com/pr/journal/v32/n2/full/pr1992164a.html
Abstract/Summary:
Human Lactobacillus sp strain GG (Lactobacillus GG) administered during acute rotavirus diarrhea has been shown to promote clinical recovery. To elucidate the immune mechanisms behind such a favorable outcome, the ELISPOT (solid phase enzyme-linked immunospot) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used, giving indirect evidence of the immunologic events in the gut. After rehydration, 39 children with acute rotavirus diarrhea, mean age 16 (SD 6) mo, randomly received either a Lactobacillus GG fermented milk product (study group) or a pasteurized yogurt (placebo group). The duration of diarrhea was significantly shorter in the study group than in the placebo group [mean 1.1 (SD 0.6) versus 2.5 (SD 1.4) d, p = 0.001]. Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection, reflected in the IgG, IgA, and IgM Ig-secreting cell numbers. At convalescence, 90% of the study group versus 46% of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus (p = 0.006). The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense. Furthermore, specific IgA response to rotavirus is endorsed, which is possibly relevant in protection against reinfections.
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Pediatrics, Tampere, Finland
Department of Pediatrics, Central Hospital of Satakunta, Tampere, Finland
Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
Title of research:
A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.
Scientific/Medical Publication:
Pediatrics 1991;88(1):91-97
Reference:
http://pediatrics.aappublications.org/content/88/1/90.abstract
Abstract/Summary:
To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (1010-11 colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (1010-11 colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P < 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea.
Researcher(s):
Raza S et al.
Research Unit(s):
Tropical Child Health Group, Liverpool School of Tropical Medicine, United Kingdom.
Title of research:
Lactobacillus GG promotes recovery from acute non-bloody diarrhoea in Pakistan.
Scientific/Medical Publication:
Pediatr Inf Dis J 1995;14:107-111
Reference:
Abstract/Summary:
A prospective, placebo-controlled, triple blind clinical trial was carried out in Pakistan to determine the effect of Lactobacillus GG on the course of acute diarrhea in hospitalized children. Forty children (mean age, 13 months) were enrolled and after rehydration received either oral Lactobacillus GG (n = 21) or placebo (n = 19) twice daily for 2 days, in addition to the usual diet. The clinical course of diarrhea was followed during the treatment period. Features on admission into the study groups were similar and were characterized by severe diarrhea, malnutrition and inappropriate management before presentation. Response was evident on Day 2 when the frequency of both vomiting and diarrhea was less in the Lactobacillus group. In those who had presented with acute nonbloody diarrhea (n = 32), the percentage of children with persistent watery diarrhea at 48 hours was significantly less in the Lactobacillus group: 31% vs. 75% (P < 0.01). No significant difference was observed by 48 hours in those presenting with bloody diarrhea. The relevance of this finding to the management of diarrhea in the tropics is discussed.
Researcher(s):
Shornikova A-V et al.
Research Unit(s):
University of Tampere, Medical School, Tampere, Finland, and University of Petrozavodsk, Karelia, Russia
Hospital of Infectious Diseases, Petrozavodsk, Karelia, Russia
Title of research:
A trial in Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea.
Scientific/Medical Publication:
Acta Paediatr 1997;86:460-465
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.1997.tb08913.x/abstract
Abstract/Summary:
In a controlled trial in Petrozavodsk, Karelia, the effects of oral rehydration and Lactobacillus strain GG (LGG) on recovery from acute diarrhoea (27% rotavirus, 21% bacterial aetiology) were studied in 123 children aged between 1 and 36 months of age. On admission to hospital, the patients were first randomized to receive either isotonic oral rehydration solution (ORS) with osmolality 311mosmol/l and sodium 90mmol/l (WHO-ORS), or a hypotonic ORS with osmolality 224mosmol/l and sodium 60mmol/l (Light-ORS), and thereafter randomized to receive either 5 × 109 colony forming units of LGG or a matching placebo. The two ORS performed equally for acute rehydration, and oral rehydration with either ORS was associated with a shorter duration of diarrhoea than intravenous rehydration (p= 0.036). Patients receiving LGG had a significantly shorter duration of watery diarrhoea [mean (SD) 2.7 (2.2) days] than those receiving the placebo [3.7 (2.8) days, p= 0.03]. LGG significantly shortened the duration of rotavirus diarrhoea but not diarrhoea with confirmed bacterial aetiology.
Researcher(s):
Canani RB et al.
Research Unit(s):
Department of Paediatrics, University of Naples Federico II, Naples, Italy
Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy
Title of research:
Probiotics for treatment of acute diarrhoea in children - randomised clinical trial of five different preparations.
Scientific/Medical Publication:
BMJ 2007;335(7615):340 doi:10.1136/bmj.39272.581736.55
Reference:
http://www.bmj.com/content/335/7615/340?view=long&pmid=17690340
Abstract/Summary:
Objective:
To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children.
Design :
Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.
Setting:
Primary care.
Participants:
Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.
Intervention:
Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.
Main outcome measures:
Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.
Results:
571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L. rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.
Conclusions:
Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.
Researcher(s):
Guandalini S et al.
Research Unit(s):
Unitá di Pediatria, Università di Catanzaro, Italy.
Title of research:
Lactobacillus GG administered in oral rehydration solution to children with acute diarrhoea: a Multicenter European Trial.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2000;30:54-60
Reference:
Abstract/Summary:
The probiotic Lactobacillus GG is effective in promoting a more rapid recovery of acute, watery diarrhea in children with rotavirus enteritis. Very limited information is available, however, on the potential role of such agents in non-rotaviral diarrheal episodes. Furthermore, no evidence is available concerning the efficacy of Lactobacillus GG administered in the oral rehydration solution during oral rehydration therapy. A multicenter trial was conducted to evaluate the efficacy of Lactobacillus GG administered in the oral rehydration solution to patients with acute-onset diarrhea of all causes.
Children 1 month to 3 years of age with acute-onset diarrhea were enrolled in a double-blind, placebo-controlled investigation. Patients were randomly allocated to group A, receiving oral rehydration solution plus placebo, or group B, receiving the same preparation but with a live preparation of Lactobacillus GG (at least 10(10) CFU/250 ml). After rehydration in the first 4 to 6 hours, patients were offered their usual feedings plus free access to the same solution until diarrhea stopped.
One hundred forty children were enrolled in group A, and 147 in group B. There were no differences at admission between the groups in age, sex, previous types of feeding, previous duration of diarrhea, use of antibiotics, weight, height, weight-height percentile, prevalence of fever, overall status, degree of dehydration, and percentage of in- versus outpatients. Duration of diarrhea after enrollment was 71.9 +/- 35.8 hours in group A versus 58.3 +/- 27.6 hours in group B (mean +/- SD; P = 0.03). In rotavirus-positive children, diarrhea lasted 76.6 +/- 41.6 hours in group A versus 56.2 +/- 16.9 hours in groups B (P < 0.008). Diarrhea lasted longer than 7 days in 10.7% of group A versus 2.7% of group B patients (P < 0.01). Hospital stays were significantly shorter in group B than in group A.
Administering oral rehydration solution containing Lactobacillus GG to children with acute diarrhea is safe and results in shorter duration of diarrhea, less chance of a protracted course, and faster discharge from the hospital.
Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial.
Researcher(s):
Canani RB et al.
Research Unit(s):
Dept. of Pediatrics, University Federico II of Naples, Italy
Title of research:
Effect of oral administration of Lactobacillus GG on the duration of diarrhea and on rotavirus excretion in ambulatory children.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 1997;24:469
Reference:
Abstract/Summary:
Background:
Oral administration of live Lactobacillus casei strain GG (LGG) has been shown effective in reducing the duration of diarrhea in hospitalized children. Aims of this work were: 1) to investigate the clinical efficacy of oral administration of LGG in ambulatory children with diarrhea, who represent the majority of children infected with Rotavirus and 2) to see whether LGG can reduce the duration of rotaviral excretion.Patients and methods. Duration of diarrhea was recorded in 100 children seen by family pediatricians and randomly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized LGG. Rotavirus was looked for in the stools of all children and, in those who were positive, it was searched again six days after the onset of diarrhea.
Results:
61 children were positive for Rotavirus and 39 were negative. Oral administration of LGG was associated with significant reduction of the duration of diarrhea in Rotavirus-positive patients (6.2 ± 0.2 vs 3.0 ± 0.2 days, p< 0.01). LGG was also effective in children with Rotavirus-negative diarrhea (5.7 ± 0.1 vs 3.2 ± 0.2 days, p < 0.01).Six days after the onset of diarrhea, only 4 out of 31 children that received LGG were still positive for Rotavirus compared to 25 out of 30 controls (p<0.01).
Conclusions:
Oral administration of LGG is effective in Rotavirus-positive as well as in Rotavirus-negative children with diarrhea needing ambulatory care. These data also provide the first evidence that LGG reduces the duration of rotaviral excretion.
Researcher(s):
Guarino A et al.
Research Unit(s):
Department of Pediatrics, University Federico II of Naples, Italy
Title of research:
Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 1997;25:516-519
Reference:
http://www.waya.pt/fileadmin/medis/waya.eu/documents/6.Guarino_-_Oral_Bacterial_Therapy_
Reduces_the_Duration_of_Symptoms_and_of_Viral_Excretion_in_Children.pdf
Abstract/Summary:
Background:
Oral administration of live Lactobacillus casei strain GG is associated with the reduction of duration of diarrhea in children admitted to the hospital because of diarrhea. The purposes of this work were to investigate the clinical efficacy of oral administration of Lactobacillus in children with mild diarrhea who were observed as outpatients, and to see whether Lactobacillus GG can reduce the duration of rotavirus excretion.
Methods:
Duration of diarrhea was recorded in 100 children seen by family pediatricians and randomly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized Lactobacillus casei, strain GG. Rotavirus was looked for in the stools of all children and in those in whom results were positive, stools were examined again 6 days after the onset of diarrhea.
Results:
In 61 children results were positive for rotavirus and in 39 results were negative. Duration of diarrhea was reduced from 6 to 3 days in children receiving Lactobacillus GG, with a similar pattern in rotavirus-positive and -negative children. Six days after the onset of diarrhea, stools in only 4 out of 31 children that received Lactobacillus GG were positive for rotavirus compared with positive findings in 25 out of 30 control subjects.
Conclusions:
Oral administration of Lactobacillus GG is effective in rotavirus-positive and rotavirus-negative ambulatory children with diarrhea. Furthermore, it reduces the duration of rotavirus excretion.
Researcher(s):
Rautanen T et al.
Research Unit(s):
Department of Paediatrics, Jorvi Hospital, Turuntie 150, FIN 02740 Espoo, Finland
Department of Paediatrics, University of Turku, Turku, Finland
Department of Paediatrics, Helsinki University Hospital, Helsinki, Finland
University of Tampere, Medical School, Tampere, Finland
Title of research:
Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillus strain GG.
Scientific/Medical Publication:
Arch Dis Child 1998;79:157-160
Reference:
http://adc.bmj.com/content/79/2/157.long
Abstract/Summary:
Two hypotonic oral rehydration solutions with osmolarities of 224 mosmol/l (Na+ 60 mmol/l, glucose 84 mmol/l) and 204 mosmol/l (Na+ 60 mmol/l, glucose 64 mmol/l), respectively, and oral treatment with Lactobacillus GG were evaluated in a double blind trial in children aged 6–36 months hospitalised for acute diarrhoea. Early administration ofLactobacillus GG at the start of oral rehydration resulted in the shortest duration of diarrhoea, best weight gain, and fastest correction of acidosis. A reduced osmolarity oral rehydration solution (224 mosmol/l) combined with early administration of Lactobacillus GG is an effective treatment for acute diarrhoea in young children; further reduction of osmolarity may not be beneficial.
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Clinical Nutrition University of Kuopio Finland
Department of Physiology, University of Kuopio, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Finland
Department of Clinical Medicine, University of Tampere, Tampere, Finland
Title of research:
Oral bacteriotherapy for viral gastroenteritis.
Scientific/Medical Publication:
Dig Dis Sci 1994;39(12):2595-2600
Reference:
http://link.springer.com/article/10.1007%2FBF02087695
Abstract/Summary:
The effect of orally administered lactobacilli on acute rotavirus diarrhea was tested in 42 well-nourished children ages 5–28 months. After oral rehydration, the patients were randomized to a study group, receiving humanLactobacillus casei strain GG 1010 colony-forming units twice daily for five days, or a control group not given lactobacilli.Lactobacillus GG was found in the feces in 83% of the study group. The diarrheal phase was shortened in that group. Dietary supplementation with lactobacilli significantly influenced the bacterial enzyme profile: urease activity during diarrhea transiently increased in the control group but not in the study group;F=8.6,P=0.01. No intergroup differences were found in -glucuronidase, -glucosidase, and glycocholic acid hydrolase levels. We suggest that rotavirus infection gives rise to biphasic diarrhea, the first phase being an osmotic diarrhea and the second associated with overgrowth of specifically urease-producing bacteria. Oral bacteriotherapy appears a promising means to counteract the disturbed microbial balance.
Researcher(s):
Piescik-Lech M et al.
Research Unit(s):
Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw, Poland
Title of research:
Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a double-blind, randomized controlled trial.
Scientific/Medical Publication:
Eur J Pediatr 2013;172:247-253
Reference:
http://link.springer.com/article/10.1007%2Fs00431-012-1878-2
Abstract/Summary:
Diarrhea treatment with either Lactobacillus GG (LGG) or smectite as an adjuvant to standard rehydration therapy has proven efficacy. In countries where both LGG and smectite are available, concomitant use is frequently practiced. We investigated whether LGG plus smectite is superior to LGG alone in the management of children with acute gastroenteritis (AGE). A double-blind, placebo-controlled, randomized trial was performed. Children aged 4 to 60 months with AGE received LGG 6 × 109 colony forming units/day plus randomly either smectite (3 g) or placebo as an adjuvant to the standard rehydration therapy. Of the 88 children randomized, 81 (92 %) were available for intention-to-treat analysis. The duration of diarrhea in the LGG/smectite group (n = 44) compared with the LGG/placebo group (n = 37) was similar (P = 0.43). There were no significant differences between the study groups for the secondary outcomes, with three exceptions. On day 4, in the LGG/placebo group compared to the LGG/smectite group, there was significantly reduced stool frequency (P = 0.03). While there was a significant (P = 0.05) difference in stool consistency on the Bristol Stool Form Scale on day 4, it was not of clinical relevance. Finally, in the LGG/smectite group compared to the LGG/placebo group, there was a significantly shorter duration of intravenous therapy after randomization (P = 0.02). No adverse events were observed in the study groups. Conclusion: LGG plus smectite and LGG alone are equally effective for treating young children with AGE. Combined use of the two interventions is not justified.
Researcher(s):
Szajewska H et al.
Research Unit(s):
Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
Title of research:
Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2007;25:871-881
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/apt.12403/abstract
Abstract/Summary:
Background:
The efficacy of each probiotic should be evaluated separately. Previously, we have shown that Lactobacillus GG (LGG) is effective in treating acute gastroenteritis (AGE) in children.
Aim:
To update our 2007 meta-analysis on the effectiveness of LGG in treating AGE in children.
Methods:
The Cochrane Library, MEDLINE and EMBASE databases were searched from August 2006 (end date of last search) to May 2013, with no language restrictions, for randomised controlled trials (RCTs) and meta-analyses.
Results:
Fifteen RCTs (2963 participants) met the inclusion criteria in this updated meta-analysis. Combined data from 11 RCTs (n = 2444) showed that LGG significantly reduced the duration of diarrhoea compared with placebo or no treatment (mean difference, MD −1.05 days, 95% CI −1.7 to −0.4). LGG was more effective when used at a daily dose ≥1010 CFU (eight RCTs, n = 1488, MD −1.11 days, 95% CI −1.91 to −0.31) than when used at a daily dose<1010 CFU (three RCTs, n = 956, MD −0.9 day, 95% CI −2.5 to 0.69). LGG was effective in children treated in Europe (five RCTs, n = 744, MD −1.27 days, 95% CI −2.04 to −0.49); in the non-European setting, the difference between the LGG group and the control group was of a borderline statistical significance (six RCTs, n = 1700, MD −0.87, 95% CI −1.81 to 0.08).
Conclusions:
Lactobacillus GG reduces the duration of diarrhoea. A subset of patients that is more likely to benefit includes subjects treated with a high daily dose of LGG (≥1010 CFU/day) who are either in-patients or out-patients from geographical Europe. Given the methodological limitations of many of the included trials, the evidence should be viewed with caution.
Researcher(s):
Van Niel CW et al.
Research Unit(s):
Sea Mar Community Health Center, Seattle, Washington, USA
Department of Pediatrics, University of Washington, Seattle, Washington, USA
Child Health Institute, University of Washington, Seattle, Washington, USA
Title of research:
Lactobacillus therapy for acute infectious diarrhea in children : A meta-analysis.
Scientific/Medical Publication:
Pediatrics 2002;109:678-684
Reference:
http://pediatrics.aappublications.org/content/109/4/678.abstract
Abstract/Summary:
Objective:
Childhood diarrhea accounts for substantial morbidity and mortality worldwide. Multiple studies in children have shown that Lactobacillus, administered orally, may have antidiarrheal properties. We conducted a meta-analysis of randomized, controlled studies to assess whether treatment with Lactobacillus improves clinical outcomes in children with acute infectious diarrhea.
Methods:
Studies were sought in bibliographic databases of traditional biomedical as well as complementary and alternative medicine literature published from 1966 to 2000. Search terms were “competitive inhibition,” “diarrhea,” “gastroenteritis,” “Lactobacillus,” “probiotic,” “rotavirus,” and “yog(h)urt.” We included studies that were adequately randomized, blinded, controlled trials in which the treatment group received Lactobacillus and the control group received an adequate placebo and that reported clinical outcome measures of diarrhea intensity. These inclusion criteria were applied by blind review and consensus. The original search yielded 26 studies, 9 of which met the criteria. Multiple observers independently extracted study characteristics and clinical outcomes. Data sufficient to perform meta-analysis of the effect of Lactobacillus on diarrhea duration and diarrhea frequency on day 2 were contained in 7 and 3 of the included studies, respectively.
Results:
Summary point estimates indicate a reduction in diarrhea duration of 0.7 days (95% confidence interval: 0.3–1.2 days) and a reduction in diarrhea frequency of 1.6 stools on day 2 of treatment (95% confidence interval: 0.7–2.6 fewer stools) in the participants who received Lactobacillus compared with those who received placebo. Details of treatment protocols varied among the studies. A preplanned subanalysis suggests a dose-effect relationship.
Conclusion:
The results of this meta-analysis suggest that Lactobacillus is safe and effective as a treatment for children with acute infectious diarrhea.
Researcher(s):
Wu S et al.
Research Unit(s):
Department of Biochemistry, Rush University, Cohn Research Building, Chicago, IL, USA
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Integrated Life Science Building, VA, USA
Title of research:
Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine.
Scientific/Medical Publication:
Gut Pathogens 2013;5(1):22
Reference:
http://www.gutpathogens.com/content/5/1/22
Abstract/Summary:
Background:
Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets.
Methods:
We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection.
Results:
We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.
Conclusion:
Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.
Researcher(s):
Hudault S et al.
Research Unit(s):
CJF 94.07 INSERM, UPR de Pharmacie Paris XI, Chatenay-Malabry, France.
Title of research:
Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain GG) against Salmonella typhimurium C5 infection.
Scientific/Medical Publication:
App Environ Microbiol 1997;63:513-18
Reference:
http://aem.asm.org/content/63/2/513.long
Abstract/Summary:
The aim of this study was to compare the antagonistic properties of Lactobacillus casei GG exerted in vitro against Salmonella typhimurium C5 in a cellular model, cultured enterocyte-like Caco-2 cells, to those exerted in vivo in an animal model, C3H/He/Oujco mice. Our results show that a 1-h contact between the invading strain C5 and either the culture or the supernatant of L. casei GG impeded the invasion by the Salmonella strain in Caco-2 cells, without modifying the viability of the strain. After neutralization at pH 7, no inhibition of the invasion by C5 was observed. The antagonistic activity of L. casei GG was examined in C3H/He/Oujco mice orally infected with C5 as follows: (i) L. casei GG was given daily to conventional animals as a probiotic, and (ii) it was given once to germ-free animals in order to study the effect of the population of L. casei GG established in the different segments of the gut. In vivo experiments show that after a single challenge with C5, this strain survives and persists at a higher level in the feces of the untreated conventional mice than in those of the treated group. In L. casei GG germ-free mice, establishment of L. casei GG in the gut significantly delayed the occurrence of 100% mortality of the animals (15 days after C5 challenge versus 9 days in germ-free mice [P < 0.01]). Cecal colonization level and translocation rate of C5 to the mesenteric lymph nodes, spleen, and liver were significantly reduced during the first 2 days post-C5 challenge, although the L. casei GG population level in the gut dramatically decreased in these animals.
Researcher(s):
Zhang Z et al.
Research Unit(s):
Department of Laboratory Medicine, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Division of Life Sciences, Graduate School at Shenzhen, Center for Biomedicine and Biotechnology, Tsinghua University, Shenzhen, China
Department of Gastroenterology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Title of research:
Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model.
Scientific/Medical Publication:
Pathog Dis 2013;67(3):184-191
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/2049-632X.12030/abstract;jsessionid=9162FEF5
C6AEA764970CE252DBC97CEB.f03t03?deniedAccessCustomisedMessage=&userIs
Abstract/Summary:
Group A human rotaviruses (RV) are a leading cause of severe dehydration and gastroenteritis in infants and young children. A large body of evidence suggests that Lactobacillus rhamnosus GG (LGG) has an effect on the incidence and severity of acute RV-induced diarrhoea; however, the timing and dosage of LGG treatment remains controversial. In the present study, a neonatal mouse model with human RV-induced diarrhoea was set up and the pathophysiological characteristics of the animals were examined. Our results indicated that RV-infected mice developed diarrhoea, accompanied by increased secretion of intestinal mucosa sIgA and serum interferon (IFN)-γ, tumour necrosis factor (TNF)-α, as well as decreased serum IgA. In addition, epithelium vacuolation was noticed in the jejunum microvillus of RV-infected mice. After intragastric administration of low (2 × 105 CFU), middle (2 × 107 CFU) or high (2 × 109 CFU) levels of LGG for four consecutive days before or after RV infection respectively, the RV-infected mice showed a shortened duration of diarrhoea and decreased epithelium vacuolation in the jejunum. Administration of a high dose of LGG before the RV infection was found to have better protective effects against RV infection than other regimens. This study demonstrates that the protective effects of LGG against RV-induced diarrhoea are highly correlated with the timing and dosage of LGG administration in neonatal mice.
Researcher(s):
Mack DR et al.
Research Unit(s):
Combined Section of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
Center for Human Nutrition, University of Nebraska Medical Center, Omaha, Nebraska, USA
Eppley Science and Allied Health, University of Nebraska Medical Center, Omaha, Nebraska, USA
Title of research:
Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.
Scientific/Medical Publication:
Am J Physiol 1999:276(4):G941-950
Reference:
http://ajpgi.physiology.org/content/276/4/G941
Abstract/Summary:
Probiotic agents, live microorganisms with beneficial effects for the host, may offer an alternative to conventional antimicrobials in the treatment and prevention of enteric infections. The probiotic agents Lactobacillus plantarum 299v and Lactobacillus rhamnosus GG quantitatively inhibited the adherence of an attaching and effacing pathogenic Escherichia coli to HT-29 intestinal epithelial cells but did not inhibit adherence to nonintestinal HEp-2 cells. HT-29 cells were grown under conditions that induced high levels of either MUC2 or MUC3 mRNA, but HEp-2 cells expressed only minimal levels of MUC2 and no MUC3 mRNA. Media enriched for MUC2 and MUC3 mucin were added exogenously to binding assays and were shown to be capable of inhibiting enteropathogen adherence to HEp-2 cells. Incubation of L. plantarum 299v with HT-29 cells increased MUC2 and MUC3 mRNA expression levels. From these in vitro studies, we propose the hypothesis that the ability of probiotic agents to inhibit adherence of attaching and effacing organisms to intestinal epithelial cells is mediated through their ability to increase expression of MUC2 and MUC3 intestinal mucins.
Researcher(s):
Vlasova AN et al.
Research Unit(s):
The Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Veterinary Preventive Medicine Department, The Ohio State University, Wooster, Ohio, United States of America
Virginia Polytechnic Institute and State University, United States of America
Title of research:
Lactobacilli and Bifidobacteria Promote Immune Homeostasis by Modulating Innate Immune Responses to Human Rotavirus in Neonatal Gnotobiotic Pigs.
Scientific/Medical Publication:
PLoS One 2013;8(10):e76962.
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788735/
Abstract/Summary:
The effects of co-colonization with Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) on 3-dose vaccination with attenuated HRV and challenge with virulent human rotavirus (VirHRV) were assessed in 4 groups of gnotobiotic (Gn) pigs: Pro+Vac (probiotic-colonized/vaccinated), Vac (vaccinated), Pro (probiotic-colonized, non-vaccinated) and Control (non-colonized, non-vaccinated). Subsets of pigs were euthanized pre- [post-challenge day (PCD) 0] and post (PCD7)-VirHRV challenge to assess diarrhea, fecal HRV shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and Vac groups were completely protected from diarrhea; protection rates against HRV shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and virus shedding were significantly higher in Controls, compared to all other groups, coincident with significantly higher serum interferon-alpha levels post-challenge. LGG+Bb12 colonization ±vaccine promoted immunomaturation as reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing mononuclear cells (MNCs) and conventional dendritic cells in intestinal tissues and blood post-challenge. Colonization decreased frequencies of toll-like receptors (TLR) 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac) pre-challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post-challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4 down-regulation) and antiviral (TLR3 up-regulation by HRV dsRNA) actions via TLR signaling. Probiotic colonization alone (Pro) increased frequencies of intestinal and systemic apoptotic MNCs pre-challenge, thereby regulating immune hyperreactivity and tolerance. However, these frequencies were decreased in intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis. Additionally, post-challenge, Pro+Vac and Pro groups had significantly decreased MNC proliferation, suggesting that probiotics control excessive lymphoproliferative reactions upon VirHRV challenge. We conclude that in the neonatal Gn pig disease model, selected probiotics contribute to immunomaturation, regulate immune homeostasis and modulate vaccine and virulent HRV effects, thereby moderating HRV diarrhea.
Researcher(s):
Ventola H et al.
Research Unit(s):
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
Toxis Ltd Oy, Lemminkäisenkatu 14-18 C, Turku, Finland
Intestinal Viruses Unit, National Institute for Health and Welfare, Helsinki, Finland
Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki, Finland
Title of research:
Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in neonatal rats.
Scientific/Medical Publication:
World Gastroenterol 2012;18:5925-5931
Reference:
http://www.wjgnet.com/1007-9327/full/v18/i41/5925.htm
Abstract/Summary:
Aim:
To study the effects of live and dead Lactobacillus rhamnosus GG (GG) on rotavirus infection in a neonatal rat model.
Methods:
At the age of 2 d, suckling Lewis rat pups were supplemented with either live or dead GG and the treatment was continued daily throughout the experiment. At the age of 5 and 6 d the pups received oral rotavirus (RV) SA-11 strain. The pups were sacrificed at the age of 7 or 8 d by decapitation. The gastrointestinal tract was removed and macroscopic observations were done. The consistency of feces in the colon was classified using a four-tier system. RV was detected from the plasma, small intestine, colon and feces by real-time quantitative polymerase chain reaction (PCR).
Results:
In this neonatal rat model, RV induced a mild-to-moderate diarrhea in all except one pup of the RV-inoculated rats. RV moderately reduced body weight development from day 6 onwards. On day 7, after 2 d of RV infection, live and dead GG groups gained significantly more weight than the RV group without probiotics [36% (P = 0.001) and 28% (P = 0.031), respectively]. In addition, when compared with the RV control group, both live and dead GG reduced the weight ratio of colon/animal body weight to the same level as in the healthy control group, with reductions of 22% (P = 0.002) and 28% (P < 0.001), respectively. Diarrhea increased moderately in both GG groups. However, the diarrhea incidence and severity in the GG groups were not statistically significantly different as compared with the RV control group. Moreover, observed diarrhea did not provoke weight loss or death. The RV control group had the largest amount of RV PCR-positive samples among the RV-infected groups, and the live GG group had the smallest amount. Rats receiving live GG had significantly less RV in the colon (P = 0.027) when compared with the RV control group. Live GG was also more effective over dead GG in reducing the quantity of RV from plasma (P = 0.047).
Conclusion:
Both live and dead GG have beneficial effects in RV infection. GG may increase RV clearance from the body and reduce colon swelling.
Researcher(s):
Hutt P et al.
Research Unit(s):
Department of Microbiology, Medical Faculty, University of Tartu, Estonia
Department of Biochemistry, Medical Faculty, University of Tartu, Estonia
Laboratory of Clinical Microbiology, United Laboratories of Tartu University Clinics, Tartu, Estonia
Title of research:
Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens.
Scientific/Medical Publication:
J Appl Microbiology 2006;100:1324-1332
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2672.2006.02857.x/abstract
Abstract/Summary:
Aim:
To develop in vitro assays for comparing the antagonistic properties and anti-oxidative activity of probiotic Lactobacillus and Bifidobacterium strains against various entero- and urinary pathogens.
Methods and Results:
The antagonistic activity of five probiotic lactobacilli (Lactobacillus rhamnosus GG, Lactobacillus fermentum ME-3, Lactobacillus acidophilus La5, Lactobacillus plantarum 299v and Lactobacillus paracasei 8700:2) and two bifidobacteria (Bifidobacterium lactis Bb12, Bifidobacterium longum 46) against six target pathogens was estimated using different assays (solid and liquid media, anaerobic and microaerobic cultivation) and ranked (low, intermediate and high). Bacterial fermentation products were determined by gas chromatography, and the total anti-oxidative activity of probiotics was measured using linolenic acid test. Pyelonephritic Escherichia coli was highly suppressed by GG and both bifidobacteria strains. Lactobacilli strains 8700:2, 299v and ME-3 were the most effective against Salmonella enterica ssp. enterica in microaerobic while ME-3 and both bifidobacteria expressed high activity against Shigella sonnei in anaerobic milieu. Lact. paracasei, Lact. rhamnosus and Lact. plantarum strains showed intermediate antagonistic activity against Helicobacter pylori under microaerobic conditions on solid media. The highest anti-oxidative activity was characteristic for Lact. fermentum ME-3 (P < 0·05). No efficient antagonist against Clostridium difficile was found. The positive correlations between the pH, lactic acid production and anti-microbial activity for all tested probiotics were assessed.
Conclusions:
Developed experimental assays enable to compare the anti-microbial and -oxidative activity of Lactobacillus and/or Bifidobacterium probiotics, which have been claimed to possess the ability of suppressing the growth of various enteric and urinary pathogens.
Significance and Impact of the Study:
Screening Lactobacillus and Bifidobacterium sp. strains according to their activity in various environmental conditions could precede the clinical efficacy studies for adjunct treatment with probiotics in cure of different gastrointestinal and urinary tract infections.
Researcher(s):
Fayol-Messaoudi D et al.
Research Unit(s):
Institut National de la Santé et de la Recherche Médicale, Unité 510, Pathogènes et Fonctions des Cellules Epithéliales Polarisées, Faculté de Pharmacie, Université Paris XI, Chātenay-Malabry, France
Title of research:
pH-, lactic acid-, and non-lactic acid-dependent activities of probiotic lactobacilli against Salmonella enterica serovar typhimurium.
Scientific/Medical Publication:
Appl Environ Microb 2005;71(10):6008-6013
Reference:
http://aem.asm.org/content/71/10/6008.long
Abstract/Summary:
The mechanism(s) underlying the antibacterial activity of probiotic Lactobacillus strains appears to be multifactorial and includes lowering of the pH and the production of lactic acid and of antibacterial compounds, including bacteriocins and nonbacteriocin, non-lactic acid molecules. Addition of Dulbecco's modified Eagle's minimum essential medium to the incubating medium delays the killing activity of lactic acid. We found that the probiotic strains Lactobacillus johnsonii La1, Lactobacillus rhamnosus GG, Lactobacillus casei Shirota YIT9029, L. casei DN-114 001, and L. rhamnosus GR1 induced a dramatic decrease in the viability of Salmonella enterica serovar Typhimurium SL1344 mainly attributable to non-lactic acid molecule(s) present in the cell-free culture supernatant (CFCS). These molecules were more active against serovar Typhimurium SL1344 in the exponential growth phase than in the stationary growth phase. We also showed that the production of the non-lactic acid substance(s) responsible for the killing activity was dependent on growth temperature and that both unstable and stable substances with killing activity were present in the CFCSs. We found that the complete inhibition of serovar Typhimurium SL1344 growth results from a pH-lowering effect.
Researcher(s):
Carey CM et al.
Research Unit(s):
Agriculture and Agri-Food Canada, Guelph Food Research Center, Guelph, Ontario, Canada
Title of research:
The effect of probiotics and organic acids on Shiga-toxin 2 gene expression in enterohemorrhagic Escherichia coli 0157:H7.
Scientific/Medical Publication:
J Microbiol Methods 2008;73(2):125-132
Reference:
http://www.sciencedirect.com/science/article/pii/S0167701208000341
Abstract/Summary:
Probiotics are known to have an inhibitory effect against the growth of various foodborne pathogens, however, the specific role of probiotics in Shiga-toxin-producing Escherichia coli (STEC) virulence gene expression has not been well defined. Shiga toxins are members of a family of highly potent bacterial toxins and are the main virulence marker for STEC. Shiga toxins inhibit protein synthesis in eukaryotic cells and play a role in hemorrhagic colitis and hemolytic uremic syndrome. STEC possesses Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2), both of which have A and B subunits. Although STEC containing both Stx1 and Stx2 has been isolated from patients with hemorrhagic colitis, Stx2 is more frequently associated with human disease complications. Thus, the effect of Lactobacillus, Pediococcus, and Bifidobacterium strains on stx2A expression levels in STEC was investigated. Lactic acid bacteria and bifidobacteria were isolated from farm animals, dairy, and human sources and included L. rhamnosus GG, L. curvatus, L. plantarum, L. jensenii, L. acidophilus, L. casei, L. reuteri, P. acidilactici, P. cerevisiae, P. pentosaceus, B. thermophilum, B. boum, B. suis and B. animalis. E. coli O157:H7 (EDL 933) was coincubated with sub-lethal concentrations of each probiotic strain. Following RNA extraction and cDNA synthesis, relative stx2A mRNA levels were determined according to a comparative critical threshold (Ct) real-time PCR. Data were normalized to the endogenous control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the level of stx2A expression between treated and untreated STEC was compared. Observed for all probiotic strains tested, stx2A was down-regulated, when compared to the control culture. Probiotic production of organic acids, as demonstrated by a decrease in pH, influenced stx2A gene expression.
Researcher(s):
Marianelli C et al.
Research Unit(s):
Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy
Title of research:
Evaluation of antimicrobial activity of probiotic bacteria against Salmonella enterica subsp. enterica serovar Typhimurium 1344 in a common medium under different environmental conditions.
Scientific/Medical Publication:
Res Microbiol 2010;161(8):673-680
Reference:
http://www.sciencedirect.com/science/article/pii/S0923250810001464
Abstract/Summary:
The importance of probiotics in human nutrition has been gaining recognition in recent years. These organisms have been shown to promote human health by enhancing immunological and digestive functions and fighting respiratory tract infections. We propose an improved in vitro model for the study of probiotic antimicrobial activity against enteropathogens, by attempting to re-create, in a common culture medium, environmental growth conditions comparable to those present in the small intestine. A preliminary experiment was carried out in order to find a culture medium able to support both probiotics and pathogens. This was done with the aim of obtaining correct assessment of the interaction under shared growth conditions. BHI medium was selected as the common culture medium and was therefore used in antimicrobial activity assays. The interactions between Salmonella 1344 and Lactobacillus rhamnosus and Lactobacillus reuteri were then assessed at different pH and oxygen availability conditions mimicking the small intestinal environment. L. rhamnosus GG ATCC 53103 (LGG) had the strongest antimicrobial effect, in particular under anaerobic conditions and at lower pH levels. Its antagonistic activity involved both lactic acid and secreted non-lactic acid molecules. Our findings suggest that each probiotic strain has an optimum range of action and should therefore be thoroughly investigated to optimize its use.
Researcher(s):
Roselli M et al.
Research Unit(s):
Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN) Via Ardeatina, Rome, Italy
Title of research:
Probiotic bacteria Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG protect intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenic Escherichia coli K88.
Scientific/Medical Publication:
Br J Nutr 2006;95:1171-84
Reference:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=920784
Abstract/Summary:
Probiotic bacteria may provide protection against intestinal damage induced by pathogens, but the underlying mechanisms are still largely unknown. We investigated whether Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG (LGG) protected intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenic Escherichia coli (ETEC) K88, by inhibiting pathogen attachment to the cells, which is the first step of ETEC pathogenicity, and regulating neutrophil recruitment, a crucial component of inflammation. A partial reduction of ETEC adhesion was exerted by probiotics and their culture supernatant fractions either undigested or digested with proteases. ETEC viability was unaffected by the presence of B. animalis, LGG or their supernatant fractions in the culture medium, indicating an absence of probiotic bactericidal activity. Probiotics and their supernatant fractions, either undigested or digested with proteases, strongly inhibited the neutrophil transmigration caused by ETEC. Both B. animalis and LGG counteracted the pathogen-induced up regulation of IL-8, growth-related oncogene-α and epithelial neutrophil-activating peptide-78 gene expression, which are chemokines essential for neutrophil migration. Moreover, the probiotics prevented the ETEC-induced increased expression of IL-1β and TNF-α and decrease of transforming growth factor-α, which are regulators ofchemokine expression. These results indicate that B. animalisMB5 and LGG protect intestinal cells from the inflammation-associated response caused by ETEC K88 by partly reducing pathogen adhesion and by counteracting neutrophil migration, probably through the regulation of chemokine and cytokine expression.
Researcher(s):
Toki S et al.
Research Unit(s):
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo,
R&D Center, Nippon Meat Packers, Inc., Tsukuba, Japan
Department of Pediatrics, Kochi Medical School, Kochi, Japan
Title of research:
Lactobacillus rhamnosus GG and Lactobacillus casei suppress Escherichia coli-induced chemokine expression in intestinal epithelial cells.
Scientific/Medical Publication:
Int Arch Allergy Immunol. 2008 Aug 21;148(1):45-58
Reference:
http://www.karger.com/Article/FullText/151505
Abstract/Summary:
Background: Recently, some strains of lactic acid bacteria (LAB) have been reported to prevent the development of atopic dermatitis and to improve allergic symptoms, especially in young children. However, the mechanisms involved in these effects are not fully understood. Intestinal microbiota play critical roles in the development of host immune development and are recognized and regulated by the host through intestinal epithelial cells (IECs). We thus hypothesized that LAB influence the host immune system through the activation of IECs. To begin testing this hypothesis, chemokine expression in IECs exposed to intestinal bacteria was investigated. Methods: Caco-2 cell monolayers were stimulated with different concentrations of various live or heat-killed intestinal bacteria or bacterial components for up to 3 h. Changes in the gene expressions of various chemokines were measured using quantitative real-time PCR. Results: The expressions of CCL20, CXCL8, CXCL10 and CX3CL1 were strongly induced by nonpathogenic Escherichia coli in a dose-dependent manner and were partially induced by some commensal LAB. In contrast, Lactobacillus rhamnosus GG (LGG) and Lactobacillus casei did not induce these chemokine expressions. In addition, LGG significantly suppressed the expressions of CCL20 and CXCL10 induced by E. coli, peptidoglycan or flagellin when cultured simultaneously. Conclusions:LGG and L. casei markedly suppressed E. coli-induced chemokine expression, presumably through the suppression of the Toll-like receptor-mediated signal transduction pathway, at least in part. The clinical importance of this suppressive effect and the mechanisms involved require further investigation; however, such effects can be used as a marker to identify clinically useful LAB.
Researcher(s):
Zhang L et al.
Research Unit(s):
College of Veterinary Medicine, China Agricultural University, Beijing, China
Police Dog Training Centre of Beijing Public Security Bureau, Beijing, China
Title of research:
Evaluation of Lactobacillus rhamnosus GG using an Escherichia coli K88 model of piglet diarrhoea: Effects on diarrhoea incidence, faecal microflora and immune responses.
Scientific/Medical Publication:
Vet Microbiol 2010;141:142–148
Reference:
http://www.sciencedirect.com/science/article/pii/S0378113509004040
Abstract/Summary:
Probiotic bacterium Lactobacillus rhamnosus GG (LGG) has been demonstrated to adhere to pig intestinal mucus, and is able to displace and inhibit pathogens, including Escherichia coli (E. coli), in vitro. However, currently there are few data concerning the effects of LGG on piglet health. The objectives of this study were to assess the effectiveness of LGG in reducing the incidence and severity of post-weaning diarrhoea in piglets, and to investigate its mechanisms of action. Eighteen weaned barrows were allocated to nonchallenged control (NCN), challenged control (CCN) and LGG treatment (LGG) groups. Diarrhoea incidence was significantly lower in group LGG than group CCN after E. coli challenge. Faecal coliform bacteria counts were significantly increased, while lactobacilli and bifidobacteria counts were decreased, in group CCN compared with the other groups after challenge. In the jejunum and ileum, secretory immunoglobin A (SIgA) concentrations were significantly higher in group LGG than in group CCN. In group LGG, administration of short-term LGG before E. coli infection attenuated the elevation of serum IL-6 induced by E. coli. Significantly higher concentrations of TNF-α were observed in group LGG than NCN and CCN at 6 h. IL-1β concentrations in group NCN were significantly higher than LGG at 6 h and higher than CCN at 24 h. In conclusion, LGG was effective in ameliorating diarrhoea in post-weaning piglets induced by E. coli K88, possibly via modulation of intestinal microflora, enhancement of intestinal antibody defence, and regulation of production of systemic inflammatory cytokines.
Researcher(s):
Burkholder KM et al.
Research Unit(s):
Molecular Food Microbiology Laboratory, Department of Food Science, 745 Agriculture Mall Drive, Purdue University, West Lafayette, Indiana, USA
Title of research:
Salmonella enterica serovar Typhimurium adhesion and cytotoxicity during epithelial cell stress is reduced by Lactobacillus rhamnosus GG.
Scientific/Medical Publication:
Gut Pathog 2009;1(1):14
Reference:
http://www.gutpathogens.com/content/1/1/14
Abstract/Summary:
Background:
Physiological stressors may alter susceptibility of the host intestinal epithelium to infection by enteric pathogens. In the current study, cytotoxic effect, adhesion and invasion of Salmonella enterica serovar Typhimurium (S. Typhimurium) to Caco-2 cells exposed to thermal stress (41°C, 1 h) was investigated. Probiotic bacteria have been shown to reduce interaction of pathogens with the epithelium under non-stress conditions and may have a significant effect on epithelial viability during infection; however, probiotic effect on pathogen interaction with epithelial cells under physiological stress is not known. Therefore, we investigated the influence of Lactobacillus rhamnosus GG and Lactobacillus gasseri on Salmonella adhesion and Salmonella-induced cytotoxicity of Caco-2 cells subjected to thermal stress.
Results:
Thermal stress increased the cytotoxic effect of both S. Typhimurium (P = 0.0001) and nonpathogenic E. coli K12 (P = 0.004) to Caco-2 cells, and resulted in greater susceptibility of cell monolayers to S. Typhimurium adhesion (P = 0.001). Thermal stress had no significant impact on inflammatory cytokines released by Caco-2 cells, although exposure to S. Typhimurium resulted in greater than 80% increase in production of IL-6 and IL-8. Blocking S. Typhimurium with anti-ShdA antibody prior to exposure of Salmonella decreased adhesion (P = 0.01) to non-stressed and thermal-stressed Caco-2 cells. Pre-exposure of Caco-2 cells to L. rhamnosus GG significantly reduced Salmonella-induced cytotoxicity (P = 0.001) and Salmonella adhesion (P = 0.001) to Caco-2 cells during thermal stress, while L. gasseri had no effect.
Conclusion:
Results suggest that thermal stress increases susceptibility of intestinal epithelial Caco-2 cells to Salmonella adhesion, and increases the cytotoxic effect of Salmonella during infection. Use of L. rhamnosus GG as a probiotic may reduce the severity of infection during epithelial cell stress. Mechanisms by which thermal stress increases susceptibility to S. Typhimurium colonization and by which L. rhamnosus GG limits the severity of infection remain to be elucidated.
Researcher(s):
Goyal N et al.
Research Unit(s):
Department of Microbiology, Panjab University, Chandigarh, India
Title of research:
Lactobacillus rhamnosus GG antagonizes Giardia intestinalis induced oxidative stress and intestinal disaccharidases: an experimental study.
Scientific/Medical Publication:
World J Microbiol Biotechnol 2013;29:1049-1057
Reference:
http://link.springer.com/article/10.1007%2Fs11274-013-1268-6
Abstract/Summary:
The present study describes the in vivo modulatory potential of Lactobacillus rhamnosus GG (LGG), an effective probiotic, in Giardia intestinalis-infected BALB/c mice. Experimentally, it was observed that oral administration of lactobacilli prior or simultaneous with Giardia trophozoites to mice, efficiently (p < 0.05) reduced both the severity and duration of giardiasis. More specifically, probiotics fed, Giardia-infected mice, showed a significant increase in the levels of antioxidants [reduced glutathione (GSH) and superoxide dismutase (SOD)] and intestinal disaccharidases [sucrase and lactase] and decreased levels of oxidants in the small intestine, in comparison with Giardia-infected mice. Histopathological findings also revealed almost normal cellular morphology of the small intestine in probiotic-fed Giardia-infected mice compared with fused enterocytes, villous atrophy and increased infiltration of lymphocytes in Giardia-infected mice. The results of the present study has shed new light on the anti-oxidative properties of LGG in Giardia mediated tissue injury, thereby suggesting that the effects of probiotic LGG are biologically plausible and could be used as an alternative microbial interference therapy.
Researcher(s):
De Keersmaecker SCJ et al.
Research Unit(s):
Centre of Microbial and Plant Genetics, K.U. Leuven, Leuven, Belgium
Title of research:
Strong antimicrobial activity of Lactobacillus rhamnosus GG against Salmonella typhimurium is due to accumulation of lactic acid.
Scientific/Medical Publication:
FEMS Microbiol Lett 2006;259:89-96
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2006.00250.x/abstract
Abstract/Summary:
Spent culture supernatant (SCS) of the probiotic Lactobacillus rhamnosus GG had been reported to exert antibacterial activity against Salmonella typhimurium. However, the chemical identity of the antimicrobial compound(s) responsible remained unknown. A survey of the antimicrobial compounds produced by L. rhamnosus GG was performed. Lactobacillus rhamnosus GG produced a low-molecular weight, heat-stable, non-proteinaceous bactericidal substance, active at acidic pH against a wide range of bacterial species. SCS of L. rhamnosus GG grown in MRS medium contained five compounds that could meet the above description, if present at the appropriate concentration. Based on different experimental approaches, it could be concluded that under the growth conditions tested, the strong antimicrobial activity of L. rhamnosus GG against Salmonella was mediated by lactic acid.
Researcher(s):
Huang JS et al.
Research Unit(s):
Children's Hospital, Boston, Massachusetts, USA
Harvard School of Public Health, Boston, Massachusetts, USA
Mount Sinai School of Medicine, New York, New York, USA
Title of research:
Efficacy of probiotic use in acute diarrhea in children- a meta-analysis.
Scientific/Medical Publication:
Dig Dis Sci 2002;47(11):2625-2634
Reference:
http://link.springer.com/article/10.1023%2FA%3A1020501202369
Abstract/Summary:
Our objective was to determine the efficacy of probiotic use in reducing the duration of increased stool output in children with acute diarrheal illness. Eligible studies were limited to trials of probiotic therapy in otherwise healthy children<5 years old with acute-onset diarrhea. The main outcome variable was difference in diarrhea duration between treatment and control groups. Our meta-analysis of 18 eligible studies suggests that coadministration of probiotics with standard rehydration therapy reduces the duration of acute diarrhea by ∼1 day [random-effects pooled estimate = −0.8 days (−1.1, −0.6), P < 0.001]. Differences in treatment effect between studies was assessed by calculating the Q statistic (Q = 204.1, P < 0.001). In subsequent analyses limited to studies of hospitalized children, to double-blinded trials, and to studies evaluating lactobacilli, the pooled estimates were similar (−0.6 to −1.2 days, P < 0.001). In conclusion, bacterial probiotic therapy shortens the duration of acute diarrheal illness in children by approximately one day.
Researcher(s):
Kaila M et al.
Research Unit(s):
Department of Pediatrics, Tampere University Hospital, Finland
lnstitute of General and Molecular Pathology, Tartu University, Estonia
Department of Biochemistry and Food Chemistry, University of Turku, Finland
Title of research:
Fecal recovery of a human Lactobacillus strain(ATCC 53103) during dietary therapy of rotavirus diarrhea in infants.
Scientific/Medical Publication:
Biosci Microflora 1998;17(2):149-151
Reference:
https://www.jstage.jst.go.jp/article/bifidus1996/17/2/17_2_149/_article
Abstract/Summary:
Human Lactobacillus strain GG (ATCC 53103) as part of the dietary therapy has been shown to shorten the duration of acute rotavirus diarrhea and to potentiate the intestinal immune response against the virus. We studied the ability of Lactobacillus GG to survive passage through the gut during rotavirus diarrhea in 29 infants, age range 5.4 to 27.5 months. After oral rehydration, they randomly received either a Lactobacillus GG formula or their normal milk ad libitum. All patients who received Lactobacillus GG became colonized with the strain as measured by fecal Lactobacillus GG counts. This result suggests that Lactobacillus GG may promote the establishment of normal intestinal microflora, even during acute gastroenteritis.
Researcher(s):
Majamaa H et al.
Research Unit(s):
Department of Clinical Medicine, University of Tampere, Finland
Valio Ltd. R&D, Helsinki, Finland
Department of Biomedical Sciences, University of Tempere, Finland
Title of research:
Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 1995;20:333-8.
Reference:
http://www.mibebesano.com.mx/pdf/Majamaa1995LGG.pdf
Abstract/Summary:
We compared different lactic acid bacteria for their effect on the immune response to rotavirus in children with acute rotavirus gastroenteritis. After initial oral rehydration, 49 children aged 6 to 35 months with rotavirus gastroenteritis randomly received either Lactobacillus casei subsp. casei strain GG (LGG), L. casei subsp. rhamnosus (Lactophilus), or a combination of Streptococcus thermophilus and L. delbrückii subsp. bulgaricus (Yalacta) twice daily for 5 days. Serum antibodies to rotavirus, total number of immunoglobulin-secreting cells (ISC), and specific antibody-secreting cells (sASC) to rotavirus were measured at the acute stage and at convalescence. The mean (SD) duration of diarrhea was 1.8 (0.8) days in children who received LGG, 2.8 (1.2) days in those receiving Lactophilus, and 2.6 (1.4) days in those receiving Yalacta (F = 3.3, p = 0.04). The ISC response was comparable in the three study groups, but the rotavirus-specific immune responses were different. LGG therapy was associated with an enhancement of IgA sASC to rotavirus and serum IgA antibody level at convalescent stage. We conclude that certain strains of lactic acid bacteria, particularly LGG, promote serum and intestinal immune responses to rotavirus, and thus may be important in establishing immunity against rotavirus reinfections.
Researcher(s):
Parker MW et al.
Research Unit(s):
Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
James M. Anderson Center for Health Systems Excellence, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
Department of Pediatrics, University of Naples “Federico II”, Naples, Italy
Title of research:
Rapid adoption of Lactobacillus rhamnosus GG for acute gastroenteritis.
Scientific/Medical Publication:
Pediatrics 2013;131:S96-S102
Reference:
http://pediatrics.aappublications.org/content/131/Supplement_1/S96.full.pdf
Abstract/Summary:
Background and Objectives:
A 2007 meta-analysis showed probiotics, specifically Lactobacillus rhamnosus GG (LGG), shorten diarrhea from acute gastroenteritis (AGE) by 24 hours and decrease risk of progression beyond 7 days. In 2005, our institution published a guideline recommending consideration of probiotics for patients with AGE, but only 1% of inpatients with AGE were prescribed LGG. The objective of this study was to increase inpatient prescribing of LGG at admission to >90%, for children hospitalized with AGE, within 120 days.
Methods:
This quality improvement study included patients aged 2 months to 18 years admitted to general pediatrics with AGE with diarrhea. Diarrhea was defined as looser or ≥3 stools in the preceding 24 hours. Patients with complex medical conditions or with presumed bacterial gastroenteritis were excluded. Admitting and supervising clinicians were educated on the evidence. We ensured LGG was adequately stocked in our pharmacies and updated an AGE-specific computerized order set to include a default LGG order. Failure identification and mitigation were conducted via daily electronic chart review and e-mail communication. Primary outcome was the percentage of included patients prescribed LGG within 18 hours of admission. Intervention impact was assessed with run charts tracking our primary outcome over time.
Results:
The prescribing rate increased to 100% within 6 weeks and has been sustained for 7 months.
Conclusions:
Keys to success were pharmacy collaboration, use of an electronic medical record for a standardized order set, and rapid identification and mitigation of failures. Rapid implementation of evidence-based practices is possible using improvement science methods.
Researcher(s):
Gunaydin G et al.
Research Unit(s):
Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden
Title of research:
Engineered Lactobacillus rhamnosus GG expressing IgG-binding domains of protein G: Capture of hyperimmune bovine colostrum antibodies and protection against diarrhoea in a mouse pup rotavirus infection model.
Scientific/Medical Publication:
Vaccine 2014;42(4)
Reference:
http://www.sciencedirect.com/science/article/pii/S0264410X13015910
Abstract/Summary:
Rotavirus-induced diarrhea causes more than 500,000 deaths annually in the world, and although vaccines are being made available, new effective treatment strategies should still be considered. Purified antibodies derived from hyperimmune bovine colostrum (HBC), from cows immunized with rotavirus, were previously used for treatment of rotavirus diarrhea in children. A combination of HBC antibodies and a probiotic strain of Lactobacillus (L. rhamnosus GG) was also found to be more effective than HBC alone in reducing diarrhea in a mouse model of rotavirus infection. In order to further improve this form of treatment, L. rhamnosus GG was engineered to display surface expressed IgG-binding domains of protein G (GB1, GB2, and GB3) which capture HBC-derived IgG antibodies (HBC-IgG) and thus target rotavirus.
The expression of IgG-binding domains on the surface of the bacteria as well as their binding to HBC-IgG and to rotavirus (simian strain RRV) was demonstrated by Western blot, flow cytometry, and electron microscopy. The prophylactic effect of engineered L. rhamnosus GG and anti-rotaviral activity of HBC antibodies was evaluated in a mouse pup model of RRV infection. The combination therapy with engineered L. rhamnosus GG (PG3) and HBC was significantly more effective in reducing the prevalence, severity, and duration of diarrhea in comparison to HBC alone or a combination of wild-type L. rhamnosus GG and HBC. The new therapy reduces the effective dose of HBC between 10 to 100-fold and may thus decrease treatment costs. This antibody capturing platform, tested here for the first time in vivo, could potentially be used to target additional gastrointestinal pathogens.
Researcher(s):
Sindhu KNC et al.
Research Unit(s):
Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Department of Public Health and Community Medicine, Tufts University School of Medicine, Massachusetts, USA
Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA
Title of research:
Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: A randomized, double-blind, pPlacebo controlled trial.
Scientific/Medical Publication:
Clin Infect Dis 2014;58(8):1107-15
Reference:
http://cid.oxfordjournals.org/content/58/8/1107.short
Abstract/Summary:
Background:
Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea.
Methods:
Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up.
Results:
Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability.
Conclusions:
LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection.
Researcher(s):
Ciccarelli S et al.
Research Unit(s):
Neonatal Intensive Care Unit, Sapienza University of Rome, Rome, Italy.
Title of research:
Management strategies in the treatment of neonatal and paediatric gastroenteritis.
Scientific/Medical Publication:
Infect Drug Resist 2013;6:133-161
Reference:
http://europepmc.org/abstract/PMC/PMC3815002
Abstract/Summary:
Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as "food supplement," seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of "doing the least": oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.
Researcher(s):
Maragkoudakis PA et al.
Research Unit(s):
University of Maribor – Faculty of Agriculture/Medical Faculty, Vrbanska, c.30/Slomškov trg 15, Maribor, Slovenia
Department of Food Science and Technology, Agricultural University of Athens, Iera Odos 75, Athens, Greece
Title of research:
Lactic acid bacteria efficiently protect human and animal intestinal epithelial and immune cells from enteric virus infection.
Scientific/Medical Publication:
Int J Food Microbiol 2010;141(S):S91-S97
Reference:
http://www.sciencedirect.com/science/article/pii/S0168160509006771
Abstract/Summary:
This study aimed to examine the potential antiviral activity of lactic acid bacteria (LAB) using animal and human intestinal and macrophage cell line models of non tumor origin. To this end, LAB strains selected on the basis of previous in vitro trials were co-incubated with cell line monolayers, which were subsequently challenged with rotavirus (RV) and transmissible gastroenteritis virus (TGEV). In order to elucidate the possible mechanism responsible for the antiviral activity, the induction of reactive oxygen species (ROS) release as well as the attachment ability of LAB on the cell lines was investigated. Various strains were found to exhibit moderate to complete monolayer protection against viral RV or TGEV disruption. Highest protection effects were recorded with the known probiotics Lactobacillus rhamnosus GG and Lactobacillus casei Shirota against both RV and TGEV, while notable antiviral activity was also attributed to Enterococcus faecium PCK38, Lactobacillus fermentum ACA-DC179, Lactobacillus pentosus PCA227 and Lactobacillus plantarum PCA236 and PCS22, depending on the cell line and virus combination used. A variable increase (of up to 50%) on the release of NO− and H2O2 (ROS) was obtained when LAB strains were co-incubated with the cell lines, but the results were found to be LAB strain and cell line specific, apart from a small number of strains which were able to induce strong ROS release in more than one cell line. In contrast, the ability of the examined LAB strains to attach to the cell line monolayers was LAB strain but not cell line specific. Highest attachment ability was observed with L. plantarum ACA-DC 146, L. paracasei subsp. tolerans ACA-DC 4037 and E. faecium PCD71. Clear indications on the nature of the antiviral effect were evident only in the case of the L. casei Shirota against TGEV and with L. plantarum PCA236 againt both RV and TGEV. In the rest of the cases, each interaction was LAB-cell line–virus specific, barring general conclusions. However, it is probable that more than one mechanism is involved in the antiviral effect described here. Further investigations are required to elucidate the underlying mode of action and to develop a cell line model as a system for selection of probiotic strains suited for farm animal applications.
Researcher(s):
Szajewska H et. al.
Research Unit(s):
Medical University of Warsaw, Department of Paediatrics, Warsaw, Poland
Department of Translational Medicine, Section of Pediatrics, University of Naples Federico II, Naples, Italy
Department of Paediatrics, Children's Hospital Zagreb, University of Zagreb School um of Medicine, Zagreb, Croatia
Department of Pediatrics, University Hospital Policlinico, University of Bari, Italy ||Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel-Aviv University, Israel
Department of Pediatrics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
Pediatric Gastroenterology and Nutrition Unit, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel.
Title of research:
Use of Probiotics for Management of Acute Gastroenteritis- A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2014;58(4):531-539
Reference:
http://europepmc.org/abstract/MED/24614141
Abstract/Summary:
The use of probiotics has been suggested in the treatment of acute gastroenteritis (AGE) in addition to early rehydration and avoidance of dietary restrictions. This document provides recommendations for the use of probiotics for the treatment of AGE in previously healthy infants and children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The GRADE system developed by the Grading of Recommendations, Assessment, Development, and Evaluations Working Group, was used to grade the strength of evidence and grades of recommendations used in these guidelines. It offers 4 categories of the quality of the evidence (high, moderate, low, and very low) and 2 categories of the strength of recommendation (strong or weak). The use of the following probiotics (in alphabetical order) may be considered in the management of children with AGE in addition to rehydration therapy: Lactobacillus rhamnosus GG (low quality of evidence, strong recommendation) and Saccharomyces boulardii (low quality of evidence, strong recommendation). Less compelling evidence is available for Lactobacillus reuteri DSM 17938 (very low quality of evidence, weak recommendation) and heat-inactivated Lactobacillus acidophilus LB (very low quality of evidence, weak recommendation). The latter, although traditionally discussed with other probiotics, does not fit with the definition of probiotics. Other strains or combinations of strains have been tested, but evidence of their efficacy is weak or preliminary.
Researcher(s):
Piescik-Lech M et al.
Research Unit(s):
Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Department of Pediatrics, University of Naples ‘Federico II’, Naples, Italy
Title of research:
Review article: the management of acute gastroenteritis in children.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2013;37(3):289-303
Reference:
Abstract/Summary:
Background:
In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society of Paediatric Infectious Disease (ESPID) developed evidence-based guidelines for the management of acute gastroenteritis (AGE) in children in Europe.
Aim:
To summarise data published subsequently to the ESPGHAN/ESPID guidelines.
Methods:
MEDLINE and The Cochrane Library were searched in August 2012 for randomised controlled trials (RCTs) or their meta-analyses published after 2008.
Results:
Efforts to improve the taste and/or efficacy of oral rehydration solution (ORS) continue, and some interventions are promising. While standard (over 24 h) nasogastric rehydration is still being used, new evidence confirms that rapid (over 4 h) rehydration is also effective. For intravenous rehydration, new evidence is available regarding rapid or ultrarapid and large-volume vs. standard-volume rehydration; as the new evidence is not consistent, until more data are available, the administration of 20 mL/kg seems appropriate. Convincing evidence has accumulated showing that ondansetron reduces the risk for vomiting; however, a clearance on safety in children is needed. New evidence has reconfirmed that in Europe, where zinc deficiency is rare, there is no benefit from the use of zinc. New data, although mainly from outside of Europe, have reconfirmed that either smectite or racecadotril is an effective adjunctive therapy to oral rehydration. There is a clear effect of using certain probiotics, such as Lactobacillus GG or S. boulardii.
Conclusions:
The update of current ESPGHAN/ESPID recommendations is warranted.
Researcher(s):
Guarino A et al.
Research Unit(s):
Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
Schneider Children's Medical Center, Tel-Aviv University, Tel-Aviv, Israel
University Paris 5 and Necker-Enfants-Malades, Paris, France
Medical University of Warsaw, Department of Pediatrics, Warsaw, Poland
Title of research:
European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases Evidence-based Guidelines for the Management of Acute Gastroenteritis in Children in Europe- Update 2014.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2014;59(1):132-52
Reference:
http://www.ncbi.nlm.nih.gov/pubmed/?term=European+Society+for+Paediatric+Gastroenter
ology%2C+Hepatology%2C+and+Nutrition%2FEuropean+Society+for+Paediatric+Infectious+Diseases+Evidence-based+Guidelines+for+the+Management+of+Acute+Gastroenteritis
+in+Children+in+Europe-+Update+2014.
Abstract/Summary:
Objectives:
These guidelines update and extend evidence-based indications for the management of children with acute gastroenteritis in Europe.
Methods:
The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir Gray system and, in parallel, with the Grading of Recommendations, Assessment, Development and Evaluations system.
Results:
Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypoosmolar solution is the major treatment and should start as soon as possible. Breast-feeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Data suggest that in the hospital setting, in non-breast-fed infants and young children, lactose-free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or racecadotril. Anti-infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an outpatients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates.
Conclusions:
Acute gastroenteritis is best managed using a few simple, well-defined medical interventions.
Researcher(s):
Marschan E et al.
Research Unit(s):
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
The Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
STAT-Consulting, Tampere, Finland
Valio Research and Development, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
The Department of Viral Diseases and Immunology, the National Public Health Institute, Helsinki, Finland
Title of research:
Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.
Scientific/Medical Publication:
Clin Exp Allergy 2008;38(4):611-618
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2008.02942.x/abstract
Abstract/Summary:
Background：
Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known.
Objective：
Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants.
Methods：
In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years.
Results：
Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use.
Conclusion：
The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.
Researcher(s):
Pelto L et al.
Research Unit(s):
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Department of Paediatrics, University of Turku, Turku, Finland
Title of research:
Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immmunostimulatory effect in healthy subjects.
Scientific/Medical Publication:
Clin Exp Allergy 1998;28:1474-1479
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2222.1998.00449.x/abstract
Abstract/Summary:
Background
Probiotic bacteria can influence immune responses both specifically by stimulating antibody production and nonspecifically by enhancing phagocytosis of pathogens and modifying cytokine production.
Objective
The authors hypothesized that probiotic bacteria can alleviate hypersensitivity by influencing phagocytes. The modulation of phagocytes may be different in healthy subjects compared with hypersensitive subjects.
Subjects and methods
In a double-blind, cross-over study, challenges with milk in milk-hypersensitive and healthy adults with or without an intestinal bacterial strain, Lactobacillus GG (ATCC 53103) were performed. The challenge-induced immunoinflammatory response was recorded by measuring the expression of phagocytosis receptors prior to and after the challenge using flow cytometry.
Results
In milk-hypersensitive subjects, milk challenge increased significantly the expression of CR1, FcγRI and FcαR in neutrophils and CR1, CR3 and FcαR in monocytes. Milk with Lactobacillus GG prevented the increase of the receptor expression. In healthy subjects, milk challenge did not influence receptor expression while milk with Lactobacillus GG increased significantly the expression of CR1, CR3, FcγRIII and FcαR in neutrophils.
Conclusion
Probiotic bacteria appear to modulate the nonspecific immune response differently in healthy and hypersensitive subjects. This is seen as an immunostimulatory effect in healthy subjects, and as a down-regulation of immunoinflammatory response in milk-hypersensitive subjects.
Researcher(s):
Piirainen L et al.
Research Unit(s):
National Public Health Institute, Laboratory for Immunobiology, Helsinki, Finland
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Valio Ltd Research Center, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki
Title of research:
Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy.
Scientific/Medical Publication:
Ann Allergy Asthma Immunol 2008;100(4):338-342
Reference:
http://www.annallergy.org/article/S1081-1206(10)60596-0/abstract
Abstract/Summary:
Background:
Lactobacillus rhamnosus GG (LGG) has demonstrated promising results in the treatment and prevention of atopic eczema.
Objective:
To study the effects of LGG on the oral immune response in adolescents and adults with birch pollen allergy combined with oral allergy syndrome.
Methods:
Patients received either LGG (n = 19) or a placebo (n = 19) for 5.5 months (from February 8 to August 6, 1999), starting 2.5 months before the birch pollen season. An oral apple challenge test was performed before, during, and after the pollen season. Saliva samples were collected before and after the challenges, and serum samples were collected before the challenges. Total IgA, IgG, and IgM and rBet v1 and rMal d1 specific IgA, IgG, IgG1, and IgG4 levels were measured from saliva with an enzyme-linked immunosorbent assay (ELISA). Serum rBet v1 specific IgE ELISA and birch radioallergosorbent testing were performed.
Results:
After 5.5 months, rBet v1 and rMal d1 specific IgA levels had increased from baseline in the LGG compared with the placebo group (Δ rBet v1 IgA, 0.319 vs −0.136 relative units; P = .02; Δ rMal d1 IgA, 0.097 vs −0.117, P = .02). rBet v1 specific IgE serum levels did not differ between the groups. In the LGG group, rBet v1 specific IgE levels correlated positively with stimulated total IgA (P = .04) and IgG (P = .003) in saliva. In the placebo group, rBet v1 specific IgE levels correlated negatively with stimulated rBet v1 and rMal d1 IgA levels (P = .009 for both) and IgG (P = .02 and P = .03, respectively).
Conclusion:
LGG showed immunostimulating effects on oral mucosa seen as increased allergen specific IgA levels in saliva.
Researcher(s):
Majamaa H et al.
Research Unit(s):
Medical School, University of Tampere, 33101 Tampere, Finland.
Department of Pediatrics, Tampere University Hospital,Tampere, Finland.
Title of research:
Probiotic: a novel approach in the management of food allergy.
Scientific/Medical Publication:
J Allergy Clin Immunol 1997;99:179-185
Reference:
http://www.jacionline.org/article/S0091-6749(97)70093-9/abstract
Abstract/Summary:
Abstract:
Background: The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier. We have previously shown that a human intestinal floral strain, Lactobacillus GG (ATCC 53103), promotes local antigen-specific immune responses (particularly in the IgA class), prevents permeability defects, and confers controlled antigen absorption.
Objective:
The aim of this study was to evaluate the clinical and immunologic effects of cow's milk elimination without (n = 14) and with (n = 13) the addition of Lactobacillus GG (5 × 108 colony-forming units/gm formula) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow's milk allergy. The second part of the study involved 10 breast-fed infants who had atopic eczema and cow's milk allergy. In this group Lactobacillus GG was given to nursing mothers.
Methods:
The severity of atopic eczema was assessed by clinical scoring. The concentrations of fecal α 1-antitrypsin, tumor necrosis factor-α, and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention.
Results:
The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG. The concentration of α 1-antitrypsin decreased significantly in this group (p = 0.03) but not in the group receiving the whey formula without Lactobacillus GG (p = 0.68). In parallel, the median (lower quartile to upper quartile) concentration of fecal tumor necrosis factor-α decreased significantly in this group, from 709 pg/gm (91 to 1131 pg/gm) to 34 pg/gm (19 to 103 pg/gm) (p = 0.003), but not in those receiving the extensively hydrolyzed whey formula only (p= 0.38). The concentration of fecal eosinophil cationic protein remained unaltered during therapy.
Conclusion:
These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy, and by alleviating intestinal inflammation, may act as a useful tool in the treatment of food allergy.
Researcher(s):
Viljanen M et al.
Research Unit(s):
The Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
Valio Research and Development, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Title of research:
Probiotic effects on faecal inflammatory markers and faecal IgA in food allergic atopic eczema/dermatitis syndrome infants.
Scientific/Medical Publication:
Pediatr Allergy Immunol 2005;16:65-71
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-3038.2005.00224.x/abstract
Abstract/Summary:
Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor-α (TNF-α), α1-antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cow's milk allergy (CMA) received in a randomized double-blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double-blind placebo-controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4-wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p = 0.064; MIX vs. placebo, p = 0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE-associated CMA infants, faecal IgA was higher for LGG than for placebo (p = 0.014), and TNF-α was lower for LGG than for placebo, but non-significantly (p = 0.111). In conclusion, 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA
Researcher(s):
Canani RB et al.
Research Unit(s):
Department of Pediatrics, University of Naples, Federico II, Naples, Italy
European Laboratory for the Investigation of Food Induced Diseases, University of Naples, Federico II, Naples, Italy
Department of Gynecology-Obstetrics and Perinatal Medicine, University of Rome, La Sapienza, Rome, Italy
Department of Pediatrics, University of Rome, La Sapienza, Rome, Italy
Neonatology and Pediatric Unit, Monaldi Hospital, Naples, Italy
Title of research:
Formula selection for management of children with cow’s milk allergy influences the rate of acquisition of tolerance-a prospective multicenter study.
Scientific/Medical Publication:
J Pediatr 2013;163:771-777
Reference:
http://www.jpeds.com/article/S0022-3476(13)00284-9/abstract
Abstract/Summary:
Objectives：
To prospectively evaluate the effect of different dietary management strategies on the rate of acquisition of tolerance in children with cow's milk allergy (CMA).
Study design：
Otherwise healthy children (aged 1-12 months) diagnosed with CMA were prospectively evaluated. The study population was divided into 5 groups based upon the formula used for management: (1) extensively hydrolyzed casein formula ([EHCF], n = 55); (2) EHCF + Lactobacillus rhamnosus GG [LGG], n = 71); (3) hydrolyzed rice formula (RHF, n = 46); (4) soy formula (n = 55); and (5) amino acid based formula (n = 33). A food challenge was performed after 12 months to assess acquisition of tolerance.
Results：
Two hundred sixty children were evaluated (167 male, 64.2%; age 5.92 months, 95% CI 5.48-6.37; body weight 6.66 kg, 95% CI 6.41-6.91; IgE-mediated CMA 111, 42.7%). The rate of children acquiring oral tolerance after 12 months was significantly higher (P < .05) in the groups receiving EHCF (43.6%) or EHCF + LGG (78.9%) compared with the other groups: RHF (32.6%), soy formula (23.6%), and amino acid based formula (18.2%). Binary regression analysis coefficient (B) revealed that the rate of patients acquiring tolerance at the end of the study was influenced by 2 factors: (1) IgE-mediated mechanism (B −2.05, OR 0.12, 95% CI 0.06-0.26; P < .001); and (2) formula choice, such that those receiving either EHCF (B 1.48, OR 4.41, 95% CI 1.44-13.48; P = .009) or EHCF + LGG (B 3.35, OR 28.62, 95% CI 8.72-93.93; P < .001).
Conclusions：
EHCF accelerates tolerance acquisition in children with CMA if compared with other dietetic choices. This effect is augmented by LGG.
Researcher(s):
Viljanen M et al.
Research Unit(s):
The Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Valio Research and Development, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
STAT-Consulting, Tampere, Finland
Title of research:
Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.
Scientific/Medical Publication:
Allergy 2005; 60: 494-500
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2004.00514.x/abstract
Abstract/Summary:
Background:
Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.
Methods:
Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants.
Results:
In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, −26.1 vs−19.8 (P = 0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup.
Conclusion:
Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.
Researcher(s):
Canani RB et al.
Research Unit(s):
Department of Pediatrics, University of Naples "Federico II,", Naples, ITALY
European Laboratory for the Investigation of Food Induced Diseases (ELFID), University of Naples "Federico II,", Naples, ITALY
Department of Women's Health and Territorial Medicine, University "La Sapienza,", Rome, ITALY
Title of research:
Effect of Lactobacillus GG on tolerance acquisition in infants with cow’s milk allergy- A randomized trial.
Scientific/Medical Publication:
J Allergy Clin Immunol 2012;129(2):580-582
Reference:
http://www.jacionline.org/article/S0091-6749(11)01569-7/abstract
Abstract/Summary:
--------
Researcher(s):
Pohjavouri E et al.
Research Unit(s):
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
Valio Research and Development, Helsinki
Department of Molecular Medicine, National Public Health Institute, Helsinki
Department of Molecular and Clinical Medicine, University of Linköping Sweden
Title of research:
Lactobacillus GG effect in increasing IFN-gamma production in infants with cow’s milk allergy.
Scientific/Medical Publication:
J Allergy Clin Immunol 2004;114(1):131-136
Reference:
http://www.jacionline.org/article/S0091-6749(04)01168-6/abstract
Abstract/Summary:
Background:
Probiotic bacteria are potentially beneficial to maturation of the infant's immune system.
Objective:
To examine the role of probiotic bacteria in treatment of cow's milk allergy (CMA) and IgE-associated dermatitis, we investigated the immunologic effects of Lactobacillus rhamnosus GG (LGG) and a mixture of 4 bacterial species (MIX).
Methods:
In a randomized, double-blind study design, concomitantly with elimination diet and skin treatment, LGG, MIX, or placebo was given for 4 weeks to infants with suspected CMA. After anti-CD3 (OKT3) and anti-CD28 stimulation of PBMCs, IFN-γ, IL-4, IL-5, and IL-12 levels were measured in culture supernatants by ELISA. Intracellular IFN-γ, IL-4, and IL-5 production on CD4 lymphocytes was analyzed with fluorescence-activated cell sorting.
Results:
Secretion of IFN-γ by PBMCs before the treatment was significantly lower in infants with CMA (P = .016) and in infants with IgE-associated CMA (P = .003) than in non-CMA infants. Among the infants who received LGG, the level of secreted IFN-γ increased in those with CMA (P = .006) and in those with IgE-associated dermatitis (P = .017) when compared with the placebo group. Secretion of IL-4 increased significantly in infants with CMA in the MIX (P = .034) but not in the LGG group.
Conclusion:
Deficiency in IFN-γ response appears to be related to CMA. LGG raises IFN-γ production of PBMC in infants with CMA and in infants with IgE-associated dermatitis and may thus provide beneficial TH1 immunomodulatory signals. MIX, although containing LGG, appears to modulate the immune responses differently.
Researcher(s):
Viljanen M et al.
Research Unit(s):
Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
Hospital for Children and Adolescents, University of Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Finland
Research Laboratory of The Hospital for Children and Adolescents, University of Helsinki, Finland
Valio Research and Development, Helsinki
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
Title of research:
Induction of inflammation as a possible mechanism of probiotic effect in atopic eczema–dermatitis syndrome.
Scientific/Medical Publication:
J Allergy Clin Immunol 2005;115:1254-1259
Reference:
http://www.jacionline.org/article/S0091-6749(05)00718-9/abstract
Abstract/Summary:
Background:
The immunomodulating mechanisms of Lactobacillus GG (LGG) and other probiotics are poorly understood.
Objective:
We studied in vivo the immunologic effects of probiotics in infants with atopic eczema–dermatitis syndrome (AEDS) and cow's milk allergy (CMA).
Methods:
Two hundred thirty infants with AEDS and suspected CMA received, concomitant with elimination diet, either LGG, a mixture of 4 probiotic strains (MIX), or placebo for 4 weeks. All available paired pretreatment and posttreatment plasma samples (n = 132) were analyzed for concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, soluble intercellular adhesion molecule 1, soluble E-selectin, TGF-β1, TGF-β2, and C-reactive protein.
Results:
In infants with IgE-associated AEDS, treatment with LGG induced higher C-reactive protein levels than in the placebo group (geometric mean, 0.83 μg/mL [95% CI, 0.56-0.81] vs 0.42 μg/mL [95% CI, 0.27-0.65]; P = .021). Concomitantly, IL-6 levels increased after treatment with LGG (P = .023) but not with MIX or placebo. Soluble E-selectin levels were higher after probiotic than after placebo treatment in infants with IgE-mediated CMA (LGG geometric mean, 86.7 ng/mL [95% CI, 75.2-100]; MIX geometric mean, 91.6 ng/mL [95% CI, 74.8-111.9]; and placebo geometric mean, 64.9 ng/mL [95% CI, 53-79.3]; analysis of covariance, P = .035; LGG vs placebo, P = .023; MIX vs placebo, P = .020). Use of MIX induced an increase in plasma IL-10 levels (P = .016).
Conclusion:
Probiotics induced systemically detectable low-grade inflammation, which might explain the clinical effects of probiotics in AEDS and CMA.
Researcher(s):
Marschan E et al.
Research Unit(s):
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
The Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
STAT-Consulting, Tampere, Finland
Valio Research and Development, Helsinki, Finland
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
The Department of Viral Diseases and Immunology, the National Public Health Institute, Helsinki, Finland
Title of research:
Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.
Scientific/Medical Publication:
Clin Exp Allergy 2008;38(4):611-618
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2008.02942.x/abstract
Abstract/Summary:
Background:
Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known.
Objective:
Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants.
Methods:
In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years.
Results:
Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use.
Conclusion:
The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.
Researcher(s):
Blumer N et al.
Research Unit(s):
Departments of Clinical Chemistry and Molecular Diagnostics
Medical Microbiology, Hospital of the Philipps University of Marburg, Berlin, Germany
Mead Johnson Nutritionals, A Bristol-Myers Squibb Company, Evansville, IN, USA
Title of research:
Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring.
Scientific/Medical Publication:
Clin Exp Allergy 2007;37:348-357
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2007.02671.x/abstract
Abstract/Summary:
Background:
Clinical studies indicate that maternal exposure to probiotic bacteria may protect from the development of allergic disease later in life.
Objective:
The purpose of this study was to analyse the effects of a perinatal Lactobacillus rhamnosus GG (LGG) supplementation on the development of allergic disorders in offspring.
Methods:
Female BALB/c mice received intragastric LGG every other day before conception, during pregnancy and lactation (perinatal supplementation group) or before conception and during pregnancy only (prenatal supplementation group). Cytokine expression of placental tissues was examined. Offspring of LGG-supplemented and sham-exposed mothers were sensitized to Ovalbumin (OVA), followed by aerosol allergen challenges. Development of experimental asthma was assessed by bronchoalveolar lavage analysis, lung histology and lung function measurement. Cytokine production of splenic mononuclear cells was analysed following in vitro stimulation.
Results:
Intestinal colonization with LGG was observed in mother mice only, but not in the offspring. However, a reduced expression of TNF-α, IFN-γ, IL-5 as well as IL-10 was observed in mice derived from perinatally LGG-supplemented mothers, whereas IL-13 and IL-4 expression remained unchanged. Moreover, in offspring of prenatally or perinatally LGG-supplemented mothers allergic airway and peribronchial inflammation as well as goblet cell hyperplasia were significantly reduced as compared with mice derived from non-supplemented mothers. In contrast, airway hyperresponsiveness to methacholine was not affected. Exposure to LGG during pregnancy only shifted the placental cytokine expression pattern with a markedly increased TNF-α level.
Conclusion:
Our data suggest that LGG may exert beneficial effects on the development of experimental allergic asthma, when applied in a very early phase of life. Immunological effects are, at least in parts, mediated via the placenta, probably by induction of pro-inflammatory cell signals.
Researcher(s):
Feleszko W et al.
Research Unit(s):
Department of Pediatric Pneumology and Allergy, The Medical University Children's Hospital, Warszawa, Poland
Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Department of Occupational Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
Title of research:
Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma.
Scientific/Medical Publication:
Clin Exp Allergy 2006;37:498-505
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2006.02629.x/abstract
Abstract/Summary:
Background:
Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far.
Objective:
The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma.
Methods:
Newborn Balb/c mice received orally 109 CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29–40) and airway challenge (days 54–56) with ovalbumin.
Results:
The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cells × 103/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-β-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes.
Conclusions:
Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-β production
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Clinical Medicine, University of Tampere, Finland
Title of research:
Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats.
Scientific/Medical Publication:
Gastroenterol 1993;105:1643-1650
Reference:
http://europepmc.org/abstract/MED/8253341
Abstract/Summary:
Background:
Lactobacilli constitute a major part of the microflora throughout the gastrointestinal tract. This study aimed to investigate the effect of lactobacilli on the gut mucosal barrier.
Methods:
Rat pups were divided into three experimental feeding groups at the age of 14 days. In addition to normal maternal milk, group "milk" received a daily gavage of cow milk, group "milk-GG" received Lactobacillus casei strain GG with cow milk, and controls were gavaged with the same volume of water. At 21 days, the absorption of horseradish peroxidase across patch-free jejunal segments and segments containing Peyer's patches was studied in Ussing chambers.
Results:
The mean absorption of intact horseradish peroxidase expressed in ng.h-1.cm-2, was significantly different in the study groups in both patch-free segments (controls, 9 [95% confidence interval, 7-12]; milk, 72 [60-87]; and milk-GG, 15 [4-52]) and in segments containing Peyer's patches (controls, 3 [1-17]; milk, 80 [43-151]; and milk-GG, 15 [4-56]). There was a significant increase in the frequency of cells secreting antibodies to beta-lactoglobulin (enzyme-linked immunospot assay) in the milk-GG group.
Conclusions:
Prolonged cow milk challenge in suckling rats increases gut permeability to intact proteins, whereas Lactobacillus GG counteracts this permeability disorder. The results suggest a link between the intensity of the antigen-specific immune response and stabilization of the mucosal barrier.
Researcher(s):
Oksaharju A et al.
Research Unit(s):
Wihuri Research Institute, Helsinki 00140, Finland
Biosystems Modelling, VTT Technical Research Centre of Finland, Espoo, Finland
Valio Ltd, Research Centre, Helsinki 00370, Finland
Medical Nutrition Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
Orion Pharma, Nonclinical R&D, Orion Corporation, Espoo 02601, Finland
Department of Vaccines and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland
Title of research:
Probiotic Lactobacillus rhamnosus downregulates FCER1 and HFH4 expression in human mast cells.
Scientific/Medical Publication:
World J Gastroenterol 2011;17(6):750-759
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042653/
Abstract/Summary:
Aim:
To investigate the effects of four probiotic bacteria and their combination on human mast cell gene expression using microarray analysis.
Methods:
Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L. rhamnosus) GG (LGG®), L. rhamnosus Lc705 (Lc705), Propionibacterium freudenreichii ssp. shermanii JS (PJS) and Bifidobacterium animalis ssp. lactis Bb12 (Bb12) and their combination for 3 or 24 h, and were subjected to global microarray analysis using an Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array.
The gene expression differences between unstimulated and bacteria-stimulated samples were further analyzed with GOrilla Gene Enrichment Analysis and Visualization Tool and MeV Multiexperiment Viewer-tool.
Result:
LGG and Lc705 were observed to suppress genes that encoded allergy-related high-affinity IgE receptor subunits α and γ (FCER1A and FCER1G, respectively) and histamine H4 receptor. LGG, Lc705 and the combination of four probiotics had the strongest effect on the expression of genes involved in mast cell immune system regulation, and on several genes that encoded proteins with a pro-inflammatory impact, such as interleukin (IL)-8 and tumour necrosis factor alpha. Also genes that encoded proteins with anti-inflammatory functions, such as IL-10, were upregulated.
Conclusion:
Certain probiotic bacteria might diminish mast cell allergy-related activation by downregulation of the expression of high-affinity IgE and histamine receptor genes, and by inducing a pro-inflammatory response.
Researcher(s):
Pessi T et al.
Research Unit(s):
Department of Paediatrics, University of Turku, Turku, Finland
Department of Microbiology and Immunology, University of Tampere, Tampere, Finland
Tampere University Hospital, Tampere, Finland
Title of research:
Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG.
Scientific/Medical Publication:
Clin Exp Allergy 2000;30:1804-1808
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2222.2000.00948.x/abstract
Abstract/Summary:
Oral Lactobacillus rhamnosus GG ingestion for 5 days to 4 weeks has been shown to alleviate clinical symptoms of gastrointestinal inflammation and atopic dermatitis.
To determine whether oral Lactobacillus rhamnosus GG may act by generating immunosuppressive mediator in atopic children.
Lactobacillus rhamnosus GG (ATCC 53103) at a daily dose of 2 × 1010 cfu was added for 4 weeks to the diets of nine children (mean age, 21 months) with atopic dermatitis. Blood and faecal samples were collected before supplementation and at early (2 weeks) and late stage (4 and 8 weeks from the beginning). The concentrations of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-α (TNFα) and interferon-γ (IFNγ) in sera, as well as the production of IL-2, IL-4, IL-10 and IFNγ in mitogen-induced peripheral blood mononuclear cells, were assessed. Secretory IgA and TNFα were also determined in faeces.
The serum IL-10 concentration differed significantly between before, early and late samples (P < 0.001) due to the elevation of serum IL-10 in the later phase of oral Lactobacillus rhamnosus GG ingestion. The enhancement of IL-10 production in mitogen-induced cultures preceded the rise in serum IL-10.
The enhanced IL-10 generation in vivo substantiates the anti-inflammatory properties of specific probiotic bacteria strains, and provides an additional reason for considering such treatments for patients with intestinal inflammation.
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Paediatrics,University of Turku, 20520 Turku, Finland
Title of research:
Modulation of the maturing gut barrier and microbiota: a novel target in allergic disease.
Scientific/Medical Publication:
Curr Pharm Des 2008;14(14):1368-1375
Reference:
http://www.eurekaselect.com/66970/article
Abstract/Summary:
The underlying denominators and treatment targets in atopic disease may be outlined as aberrant barrier functions of the skin epithelium and gut mucosa, and dysregulation of the immune response to ubiquitous environmental antigens. The route of sensitization varies with age, dietary antigens predominating in infancy. The immaturity of the immune system and the gastrointestinal barrier may explain the peak prevalence of food allergies at an early age. Dietary methods to control symptoms and reduce the risk of allergic disease have hitherto focused on elimination diets, alone or in combination with other environmental measures. The results have not been satisfactory regarding long-term prevention, primary or secondary. In view of the increasing burden of the abnormalities, new approaches are urgently needed for the management of allergic diseases and their prevention in at-risk infants. Novel methods here may include probiotics to counteract the immunological and gut mucosal barrier dysfunction associated with allergic disease, and thereby to strengthen endogenous defence mechanisms. Notwithstanding the demonstrations of important immunoregulatory potential of the well-balanced gut microbiota, the major objective health benefits of specific strains in allergic infants have only recently been clinically proven. Advances here have prompted enthusiasm in the scientific community and food industry and have fuelled research activities currently focusing firstly on identification of specific strains with anti-allergenic potential, and secondly on the question how food matrix and dietary content interact with the most efficacious probiotic strains.
Researcher(s):
Baldassarre ME et al.
Research Unit(s):
Neonatology and Neonatal Intensive Care Unit, Department of Gynecology, Obstetrics and Neonatology, University of Bari-Policlinic Hospital, Bari, Italy
Department of Internal Medicine and Public Medicine, Medical Statistics, University of Bari, Bari, Italy
Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX
Title of research:
Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone.
Scientific/Medical Publication:
J Pediatr 2009 Oct 30 PMID 19880141
Reference:
http://www.jpeds.com/article/S0022-3476(09)00885-3/abstract
Abstract/Summary:
Objectives:
To determine the benefits of Lactobacillus rhamnosus GG (LGG) in an extensively hydrolyzed casein formula (EHCF) in improving hematochezia and fecal calprotectin over EHCF alone.
Study design:
Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group. We also compared fecal calprotectin and hematochezia on 26 formula-fed infants randomly assigned to EHCF with LGG (Nutramigen LGG) (EHCF + LGG) or without (Nutramigen) (EHCF − LGG) and on 4 breastfed infants whose mothers eliminated dairy.
Results:
Fecal calprotectin in those with hematochezia was significantly higher than in comparisons (mean ± SD 325.89 ± 152.31 vs 131.97 ± 37.98 μg/g stool, t = 6.79, P < .0001). At 4 weeks, fecal calprotectin decreased to 50% of baseline but was still significantly higher than in comparisons (157.5 ± 149.13 vs 93.72 ± 36.65 μg/g, P = .03). Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF − LGG (−214.5 ± 107.93 vs −112.7 ± 105.27 μg/g, t = 2.43, P = .02). At 4 weeks, none of the EHCF + LGG had blood in stools, and 5/14 on EHCF − LGG did (P = .002).
Conclusion:
Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis. EHCF + LGG resulted in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone.
Researcher(s):
Bottcher MF et al.
Research Unit(s):
Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Department of Cellular and Microbial Biology, Division of Microbial Ecology, Karolinska Institute, Stockholm, Sweden
Department of Paediatrics, Östersund County Hospital, Östersund, Sweden
Title of research:
Microflora-associated characteristics in faeces from allergic & nonallergic infants.
Scientific/Medical Publication:
Clin Exp Allergy 2000;30:1590-1596
Reference:
Abstract/Summary:
Background:
The prevalence of allergic diseases has increased particularly over the past 30–40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation.
Objective:
The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11–18), through analysing microflora-associated biochemical markers in faeces.
Methods:
Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically.
Results:
The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups.
Conclusion:
The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora that may disturb the development of a normal Th1-/Th2-balance in allergic children
Researcher(s):
Kawase M et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Kanagawa 241-0023, Japan
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Kanagawa 228-8522, Japan
Title of research:
Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study.
Scientific/Medical Publication:
Int J Food Microbiol 2009;128(3):429-434
Reference:
http://www.sciencedirect.com/science/article/pii/S0168160508005254
Abstract/Summary:
There has been much interest in the potential of using probiotic bacteria for treating allergic diseases. A double-blind, placebo-controlled study was conducted to examine the effectiveness of Lactobacillus GG (LGG) and L. gasseri TMC0356 (TMC0356) in alleviating Japanese cedar pollinosis (JCP), a seasonal allergic rhinitis caused by Japanese cedar pollen. Fermented milk prepared with the tested bacteria or placebo yoghurt was administered to 40 subjects with a clinical history of JCP for 10 weeks. Subjective symptoms, self-care measures and blood samples were compared between the two groups. Peripheral blood mononuclear cells (PBMCs) were collected from seven patients with JCP and in vitro cytokine production by the isolated PBMCs was analysed in the presence of heat-killed lactic acid bacteria. Consumption of the fermented milk significantly decreased the mean symptom score for nasal blockage after 9 weeks (P < 0.05) and mean symptom-medication scores after 9 and 10 weeks when compared with the placebo group (P < 0.01 and P < 0.05 respectively). The tested strains of lactic acid bacteria affected cytokine production by isolated PBMCs in vitro in a strain-dependent manner. LGG significantly inhibited IL-4 and IL-5 production by PBMCs stimulated by both Cry j 1 and PHA. TMC0356 only suppressed IL-5 production stimulated by PHA. The fermented milk prepared with LGG and TMC0356 might be beneficial in JCP because of its effect on nasal blockage. The effects of LGG and TMC0356 might arise at least partly from their specific down-regulation of the human Th2 immune response.
Researcher(s):
Pessi T et al.
Research Unit(s):
Department of Paediatrics, University of Turku, FIN-20521 Turku, Finland
Department of Respiratory Medicine, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland
Department of Clinical Chemistry and Clinical Microbiology, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland
Title of research:
Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.
Scientific/Medical Publication:
International Immunopharmacology 2001;1:211-218
Reference:
http://www.sciencedirect.com/science/article/pii/S1567576900000187
Abstract/Summary:
Earlier data indicate that Lactobacillus rhamnosus GG ATCC 53103 (L. GG), a commensal intestinal bacterial strain, promotes the degradation of proteins in the gut in vivo, and bovine casein hydrolysed with L. GG-derived proteases suppresses lymphocyte proliferation in vitro. The present study aimed to evaluate the effect of L. GG-degraded bovine casein on T-cell activation, i.e. IL-2 mRNA expression and protein kinase C (PKC) translocation. To this end, Northern blot analyses for IL-2 mRNA expression and PKC assays with and without L. GG-degraded casein were carried out on T cells isolated from 11 healthy adults. Cell cultures in 8–11 experiments contained 1 mg ml−1 bovine casein in degraded or undegraded form in the presence of a mitogen, i.e. phorbol 12,13-dibutyrate plus calcium ionophore (PBDu+A23187) or anti-CD3. Also IL-2, IL-4 and IFN-γ syntheses were determined in 24-h culture supernatants. IL-2 mRNA expression was reduced in experiments with L. GG-degraded casein. In parallel, the IL-2 concentration in PBDu+A23187-stimulated culture supernatants, expressed as geometric means (95% confidence interval), decreased from 15,892 (7174–35,203) pg ml−1 to 4744 (2095–10,742) pg ml−1 when containing L. GG-degraded casein. L. GG-degraded casein inhibited PKC translocation, the action resembling that of PKC inhibitor, RO31-8220. These results extend previous data on L. GG-degraded casein, showing in vitro the suppression of T-cell activation.
Researcher(s):
Kalliomaki M et al.
Research Unit(s):
Department of Pediatrics, University of Turku, Turku, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Department of Medical Microbiology, University of Turku, Turku, Finland
Title of research:
Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.
Scientific/Medical Publication:
J Allergy Clin Immunol 2001;107:129-134
Reference:
http://www.jacionline.org/article/S0091-6749(01)97134-9/abstract
Abstract/Summary:
Background: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. Objective: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. Methods: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. Results: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P = .005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 × 107 [3.8-22.9 × 107 ] vs 3.3 × 107 [1.8-6.1 × 10 x 107], P = .04) and tended to have fewer bifidobacteria (1.8 × 109 [0.4-7.6 × 109] vs 6.1 × 109 [2.5-14.6 × 109], P = .11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P = .03). The differences were not detected by bacterial cultivation. Conclusion: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.
Researcher(s):
Sutas Y et al.
Research Unit(s):
University of Tampere, Medical School, Tampere, Finland
Agricultural Research Centre of Finland, Food Research Institute, Jokioinen, Finland
Valio Ltd, Research & Development Centre, Helsinki, Finland
University of Helsinki, Department of Food Technology, Dairy Sciences, Helsinki, Finland
Title of research:
Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG-derived enzymes.
Scientific/Medical Publication:
J Allergy Clin Immunol 1996;98:216-224
Reference:
http://www.jacionline.org/article/S0091-6749(96)70245-2/abstract
Abstract/Summary:
Background:Processing of proteins in the gut and activation of T-cell suppression leads to systemic hyporesponsiveness to ingested protein antigens. Objective:The study was designed to determine whether lactobacilli, a major part of human intestinal microflora, can contribute to degradation of food antigens in the gut and modify their immunoactivities. Methods:Lymphocyte transformation tests were carried out in healthy adults to determine the mitogen-induced lymphocyte proliferative responses to bovine caseins hydrolyzed with pepsin and trypsin and to bovine caseins additionally hydrolyzed with enzymes derived from Lactobacillus casei strain GG (ATCC 53103). Results:In experiments done with caseins hydrolyzed with pepsin and trypsin, β- and α s1-caseins significantly suppressed the proliferation of lymphocytes at 0.1 and 10 μg/ml, respectively, when compared with corresponding control cultures without these hydrolysates. In contrast, κ-casein significantly stimulated the proliferation of lymphocytes at 10 μg/ml. In experiments done with caseins additionally hydrolyzed with L. casei GG–derived enzymes, there was one consistent effect on lymphocyte proliferation: suppression by α s1-, β-, and κ-caseins at 0.1, 10, and 1000 μg/ml, respectively. Conclusions:Hydrolysis of caseins with L. casei GG–derived enzymes generates molecules with suppressive effects on lymphocyte proliferation. In addition, intestinal bacteria can be beneficial in the downregulation of hypersensitivity reactions to ingested proteins in patients with food allergy.
Researcher(s):
Kawase M et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Kanagawa, Japan
Title of research:
Orally administered Lactobacillus gasseri TMC0356 and Lactobacillus GG alleviated nasal blockage of guinea pig with allergic rhinitis.
Scientific/Medical Publication:
Microbiol Immunol 2007;51:1109-1114
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1348-0421.2007.tb04006.x/full
Abstract/Summary:
Lactobacillus GG (LGG) and L. gasseri TMC0356 (TMC0356) were investigated for their ability to alleviate nasal blockage associated with allergic rhinitis using a guinea pig model. The increases in sRaw at 10 min and 5 hr after the exposure of the nasal mucosa to OVA were significantly alleviated in the guinea pigs orally administrated with LGG and TMC0356 compared with those of the control (P<0.05 and P<0.01). The total numbers of leukocytes, particularly eosinophils and neutrophils from the nasal cavity lavage fluid, and the OVA-specific IgE concentration in the serum were also decreased in the guinea pigs orally administrated with LGG and TMC0356, although the decreases were not statistically significant. These results suggest that LGG and TMC0356 can alleviate antigen-induced nasal blockage in earlyphase and late-phase inflammatory responses associated with allergic rhinitis.
Researcher(s):
Penders J et al.
Research Unit(s):
Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University
Department of Medical Microbiology, University Hospital of Maastricht
Department of Epidemiology, Care and Public Health Research Institute (Caphri), Maastricht University, Maastricht, the Netherlands
Title of research:
The role of the intestinal microbiota in the development of atopic disorders.
Scientific/Medical Publication:
Allergy 2007;62:1223-1236
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2007.01462.x/abstract
Abstract/Summary:
The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed.
Researcher(s):
Nylund L et al.
Research Unit(s):
Functional Foods Forum, University of Turku, Turku, FI-20014, Finland
Department of Veterinary Biosciences and Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
Finnish Red Cross Blood Service, Helsinki, Finland
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
Department for Biotechnology and Biochemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
Title of research:
Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease.
Scientific/Medical Publication:
BMC Microbiology 2013;13:12
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563445/
Abstract/Summary:
Background:
Deviations in composition and diversity of intestinal microbiota in infancy have been associated with both the development and recurrence of atopic eczema. Thus, we decided to use a deep and global microarray-based method to characterize the diversity and temporal changes of the intestinal microbiota in infancy and to define specific bacterial signatures associated with eczema. Faecal microbiota at 6 and 18 months of age were analysed from 34 infants (15 with eczema and 19 healthy controls) selected from a prospective follow-up study based on the availability of faecal samples. The infants were originally randomized to receive either Lactobacillus rhamnosus GG or placebo.
Results:
Children with eczema harboured a more diverse total microbiota than control subjects as assessed by the Simpson’s reciprocal diversity index of the microarray profiles. Composition of the microbiota did not differ between study groups at age of 6 months, but was significantly different at age of 18 months as assessed by MCPP (p=0.01). At this age healthy children harboured 3 -fold greater amount of members of the Bacteroidetes (p=0.01). Microbiota of children suffering from eczema had increased abundance of the Clostridium clusters IV and XIVa, which are typically abundant in adults. Probiotic Lactobacillus rhamnosus GG supplementation in early infancy was observed to have minor long-term effects on the microbiota composition.
Conclusion:
A diverse and adult-type microbiota in early childhood is associated with eczema and it may contribute to the perpetuation of eczema.
Researcher(s):
Kirjavainen PV et al.
Research Unit(s):
Department of Biochemistry and Food Chemistry, and Functional Foods Forum, University of Turku, Turku, FINLAND
Department of Pediatrics, Turku University Hospital, Turku, FINLAND
Title of research:
Probiotic bacteria in the management of atopic disease: Underscoring the importance of viability.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2003;36:223-227
Reference:
Abstract/Summary:
Objectives:
The aim of this study was to assess the efficacy of oral supplementation of viable and heat-inactivated probiotic bacteria in the management of atopic disease and to observe their effects on the composition of the gut microbiota.
Methods:
The study population included 35 infants with atopic eczema and allergy to cow's milk. At a mean age of 5.5 months, they were assigned in a randomized double-blind manner to receive either extensively hydrolyzed whey formula (placebo group) or the same formula supplemented with viable (viable LGG group) or heat-inactivated Lactobacillus GG (heat-inactivated LGG group), respectively. The changes in symptoms were assessed by the SCORAD method and the presence of some predominant bacterial genera in the feces detected with 16S rRNA-specific probes.
Results:
The treatment with heat-inactivated LGG was associated with adverse gastrointestinal symptoms and diarrhea. Consequently, the recruitment of patients was stopped after the pilot phase. Within the study population, atopic eczema and subjective symptoms were significantly alleviated in all the groups; the SCORAD scores (interquartile range) decreased from 13 (range, 4–29) to 8 (range, 0–29) units in the placebo group, from 19 (range, 4–47) to 5 (range, 0–18) units in the viable LGG group, and from 15 (range, 0–29) to 7 (range, 0–26) units in the heat-inactivated LGG group. The decrease in the SCORAD scores within the viable LGG group tended to be greater than within the placebo group. The treatments did not appear to affect the bacterial numbers within the genera enumerated.
Conclusions:
Supplementation of infant formulas with viable but not heat-inactivated LGG is a potential approach for the management of atopic eczema and cow's milk allergy.
Researcher(s):
Sawada J et al.
Research Unit(s):
Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan
Technical Research Laboratory, Takanashi Milk Products Co. Ltd., Yokohama, Kanagawa, Japan
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Title of research:
Ingestion of heat-treated Lactobacillus rhamnosus GG prevents development of atopic dermatitis in NC/Nga mice.
Scientific/Medical Publication:
Clin Exp Allergy 2006;37:296-303
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2006.02645.x/abstract
Abstract/Summary:
Background:
Continuous oral administration of live Lactobacillus rhamnosus GG (L. GG) to pregnant subjects with atopic dermatitis and their children, suppressed the frequency of atopic dermatitis. The details of mechanisms and immune systems involved in this suppressive effect, however, remain speculative.
Objective:
We sought to clarify suppressive mechanisms of L. GG on atopic dermatitis by using NC/Nga mice, a model of human atopic dermatitis.
Methods:
Maternal mice and infant mice were fed with food containing or not containing heat-treated L. GG during pregnancy and breastfeeding, and after weaning.
Results:
Control NC/Nga mice raised under an air-uncontrolled condition spontaneously manifested typical skin lesions very similar to those in patients with atopic dermatitis. On the other hand, administration of food containing heat-treated L. GG inhibited the onset and development of atopic skin lesions, accompanied by smaller numbers of mast cells and eosinophils in the affected skin sites. Mice fed with L. GG showed a significant increase in plasma IL-10 levels compared with control mice, while there was no significant difference in the proportion of splenic CD4+CD25+ regulatory T cells between mice fed with L. GG and control mice. The IL-10 mRNA expression was enhanced in both Peyer's patches and mesenteric lymph nodes in mice fed with L. GG.
Conclusion:
These findings suggest that some components of heat-treated L. GG may have an ability to delay the onset and suppress the development of atopic dermatitis, probably through a strong induction of IL-10 in intestinal lymphoid organs and systemic levels.
Researcher(s):
Isolauri E et al.
Research Unit(s):
Department of Paediatrics,University of Turku, 20520 Turku, Finland
Title of research:
Modulation of the maturing gut barrier and microbiota:a novel target in allergic disease.
Scientific/Medical Publication:
Curr Pharm Des 2008;14(14):1368-1375
Reference:
http://www.eurekaselect.com/66970/article
Abstract/Summary:
The underlying denominators and treatment targets in atopic disease may be outlined as aberrant barrier functions of the skin epithelium and gut mucosa, and dysregulation of the immune response to ubiquitous environmental antigens. The route of sensitization varies with age, dietary antigens predominating in infancy. The immaturity of the immune system and the gastrointestinal barrier may explain the peak prevalence of food allergies at an early age. Dietary methods to control symptoms and reduce the risk of allergic disease have hitherto focused on elimination diets, alone or in combination with other environmental measures. The results have not been satisfactory regarding long-term prevention, primary or secondary. In view of the increasing burden of the abnormalities, new approaches are urgently needed for the management of allergic diseases and their prevention in at-risk infants. Novel methods here may include probiotics to counteract the immunological and gut mucosal barrier dysfunction associated with allergic disease, and thereby to strengthen endogenous defence mechanisms. Notwithstanding the demonstrations of important immunoregulatory potential of the well-balanced gut microbiota, the major objective health benefits of specific strains in allergic infants have only recently been clinically proven. Advances here have prompted enthusiasm in the scientific community and food industry and have fuelled research activities currently focusing firstly on identification of specific strains with anti-allergenic potential, and secondly on the question how food matrix and dietary content interact with the most efficacious probiotic strains.
Researcher(s):
Foolad N et al.
Research Unit(s):
Department of Dermatology, University of California at Davis School of Medicine, Sacramento, California, USA
Title of research:
Effect of nutrient supplementation on atopic dermatitis in children. A systematic review of probiotics, prebiotics, formula and fatty acids.
Scientific/Medical Publication:
Arch Dermatol 2013:149:350-355
Reference:
http://archderm.jamanetwork.com/article.aspx?articleid=1485346
Abstract/Summary:
Objective:
To identify whether nutrient supplementation with probiotics, prebiotics, formula, or fatty acids prevents the development of atopic dermatitis (AD) or reduces the severity of AD in newborns to children younger than 3 years.
Data Sources:
We searched MEDLINE, Cochrane Central Register of Controlled Trials, and LILACS (Latin American and Caribbean Health Science Literature) from January 1, 1946, to August 27, 2012, and performed an additional manual search.
Study Selection:
Randomized controlled trials and cohort studies examining nutritional supplementation in prevention and amelioration of AD among children younger than 3 years.
Data:
Extraction Of 92 articles, 21 met inclusion criteria.
Data Synthesis:
In the 21 studies, a total of 6859 participants received supplements, which included infants or mothers who were either pregnant or breastfeeding; 4134 infants or mothers served as controls. Nutritional supplementation was shown to be an effective method in preventing AD (11 of 17 studies) or decreasing its severity (5 of 6 studies). The best evidence lies with probiotics supplementation in mothers and infants in preventing development and reducing severity of AD. Specifically, Lactobacillus rhamnosus GG was effective in long-term prevention of AD development. γ-Linolenic acid reduced severity of AD. Supplementation with prebiotics and black currant seed oil (γ-linolenic acid and ω-3 combination) was effective in reducing the development of AD. Conflicting findings were reported from different research groups that performed supplementation with an amino acid–based formula.
Conclusions:
Certain types of nutrient supplementation are beneficial in preventing AD development and reducing its severity. Future research elucidating the mechanisms underlying the actions of nutritional supplementation on AD is necessary.
Researcher(s):
Barneston RStC et al.
Research Unit(s):
Department of Dermatology, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia
Department of Dermatology, New Children's Hospital, Westmead, Sydney, Australia
Title of research:
Childhood atopic eczema.
Scientific/Medical Publication:
Brit Med J 2002;324: 1376-1379
Reference:
http://www.bmj.com/content/324/7350/1376.1
Abstract/Summary:
Atopic eczema is a common condition that affects more than one in ten children in developed countries, and the incidence is increasing. There are probably several reasons for this, including higher exposure to air pollution, smaller families with less exposure to infections, more pets, higher maternal age, and a wider range of foods. There is clearly also an important hereditary component to atopic eczema. This is complex because not all affected children are atopic, though the genes implicated in atopy are likely to be involved, together with others as yet unknown. Atopic eczema usually presents during the first year of life, and when it is severe it is extremely disabling. It may also cause major psychological problems. Most affected children are also allergic to house dust mite, and this is probably a major cause of exacerbation of the condition. Probably less than 10% overall have IgE mediated food allergy, but some have late phase reactions with positive results on patch tests to foods.
Researcher(s):
Kalliomaki M et al.
Research Unit(s):
Department of Paediatrics, University of Turku and Turku University Hospital
Department of Biochemistry and Food Chemistry, University of Turku and Turku University Hospital
Department of Clinical Chemistry, University of Turku and Turku University Hospital
National Public Health Institute, Turku, Finland
Title of research:
Probiotics in primary prevention of atopic disease:a randomised, placebo-controlled trial.
Scientific/Medical Publication:
Lancet 2001;357:1076-1079
Reference:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04259-8/fulltext
Abstract/Summary:
Background:
Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in Western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy).
Methods:
In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint.
Findings:
Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0·51 [95% Cl 0·32—0·84]). The number needed to treat was 4·5 (95% Cl 2·6—15·6).
Interpretations:
Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.
Researcher(s):
Kalliomaki M et al.
Research Unit(s):
Department of Paediatrics, University of Turku, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Finland
STAT-Consulting, Tampere, Turku
National Public Health Institute, Turku
Title of research:
Probiotics and prevention of atopic disease – a 4-year follow-up of a randomised placebo-controlled trial.
Scientific/Medical Publication:
Lancet 2003;261:1869-1871
Reference:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)13490-3/fulltext
Abstract/Summary:
Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG (ATCC 53103), reduces incidence of atopic eczema in at-risk children during the first 2 years of life (infancy). We have therefore assessed persistence of the potential to prevent atopic eczema at 4 years. Atopic disease was diagnosed on the basis of a questionnaire and a clinical examination. 14 of 53 children receiving lactobacillus had developed atopic eczema, compared with 25 of 54 receiving placebo (relative risk 0·57, 95% CI 0·33—0·97). Skin prick test reactivity was the same in both groups: ten of 50 children previously given lactobacillus compared with nine of 50 given placebo tested positive. Our results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy.
Researcher(s):
Kalliomaki M et al.
Research Unit(s):
Department of Paediatrics, University of Turku, Finland
Functional Foods Forum, University of Turku, Turku, Finland
STAT Consulting, Tampere, Finland
Title of research:
Probiotics during the first 7 years of life: A cumulative risk reduction of eczema in a randomized, placebo-controlled trial.
Scientific/Medical Publication:
J Allergy Clin Immunol 2007;119:1019-1021
Reference:
http://www.jacionline.org/article/S0091-6749(06)03800-0/abstract
Abstract/Summary:
-
Researcher(s):
Rautava S et al.
Research Unit(s):
Department of Paediatrics, University of Turku. Turku, Finland
Title of research:
Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant.
Scientific/Medical Publication:
J Allergy Clin Immunol 2002;109:119-121
Reference:
http://www.jacionline.org/article/S0091-6749(02)25194-5/abstract
Abstract/Summary:
The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor β2 (TGF-β2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P = .018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P = .0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life.
Researcher(s):
Foolad N et al.
Research Unit(s):
Department of Dermatology, University of California at Davis School of Medicine, Sacramento, CA 95816, USA.
Title of research:
Effect of nutrient supplementation on atopic dermatitis in children. A systematic review of probiotics, prebiotics, formula and fatty acids.
Scientific/Medical Publication:
Arch Dermatol 2013:149:350-355
Reference:
http://archderm.jamanetwork.com/article.aspx?articleid=1485346
Abstract/Summary:
Objective:
To identify whether nutrient supplementation with probiotics, prebiotics, formula, or fatty acids prevents the development of atopic dermatitis (AD) or reduces the severity of AD in newborns to children younger than 3 years.
Data:
Sources We searched MEDLINE, Cochrane Central Register of Controlled Trials, and LILACS (Latin American and Caribbean Health Science Literature) from January 1, 1946, to August 27, 2012, and performed an additional manual search.
Study Selection:
Randomized controlled trials and cohort studies examining nutritional supplementation in prevention and amelioration of AD among children younger than 3 years.
Data:
Extraction Of 92 articles, 21 met inclusion criteria.
Data Synthesis In the 21 studies, a total of 6859 participants received supplements, which included infants or mothers who were either pregnant or breastfeeding; 4134 infants or mothers served as controls. Nutritional supplementation was shown to be an effective method in preventing AD (11 of 17 studies) or decreasing its severity (5 of 6 studies). The best evidence lies with probiotics supplementation in mothers and infants in preventing development and reducing severity of AD. Specifically, Lactobacillus rhamnosus GG was effective in long-term prevention of AD development. γ-Linolenic acid reduced severity of AD. Supplementation with prebiotics and black currant seed oil (γ-linolenic acid and ω-3 combination) was effective in reducing the development of AD. Conflicting findings were reported from different research groups that performed supplementation with an amino acid–based formula.
Conclusions:
Certain types of nutrient supplementation are beneficial in preventing AD development and reducing its severity. Future research elucidating the mechanisms underlying the actions of nutritional supplementation on AD is necessary.
Researcher(s):
Nase L et al.
Research Unit(s):
Institute of Dentistry, University of Helsinki, Finland
Title of research:
Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG in milk on dental caries risk in children.
Scientific/Medical Publication:
Caries Res 2001;35:412-420
Reference:
http://www.ncbi.nlm.nih.gov/pubmed/11799281
Abstract/Summary:
Lactobacillus rhamnosus GG, ATCC (LGG), has shown antagonism to many bacteria including mutans streptococci. This randomized, double-blind, placebo-controlled intervention study was designed to examine whether milk containing LGG has an effect on caries and the risk of caries in children when compared with normal milk. 594 children, 1-6 years old, from 18 municipal day-care centres were included. The children received the milk with meals from coded containers 5 days a week in the day-care centres for 7 months. The children's oral health was recorded at baseline and at the end, using WHO criteria. The caries risk was calculated based on clinical and microbiological data, comprising mutans streptococcus levels from dental plaque and saliva. The risk was classified as high if the child had a dmft/DMFT or initial caries score >0, and a mutans streptococcus count > or = 105 CFU/ml. The results showed less dental caries in the LGG group and lower mutans streptococcus counts at the end of the study. LGG was found to reduce the risk of caries significantly (OR = 0.56, p = 0.01; controlled for age and gender, OR = 0.51, p = 0.004). The effect was particularly clear in the 3- to 4-year-olds. Thus, milk containing the probiotic LGG bacteria may have beneficial effects on children's dental health.
Researcher(s):
Ahola AJ et al.
Research Unit(s):
Division of Nutrition, University of Helsinki, Helsinki, Finland
Institute of Dentistry, University of Helsinki, Helsinki, Finland
R&D, Valio Ltd., Helsinki, Finland
Stat-Consulting, Tampere, Finland
Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
Title of research:
Short-term consumption of probiotic-containing cheese and its effect on dental caries risk factors.
Scientific/Medical Publication:
Arch Oral Bio 2002;799-804
Reference:
http://www.aobjournal.com/article/S0003-9969(02)00112-7/abstract
Abstract/Summary:
Cheese is known to contain compounds that reduce the risk of dental caries. The long-term consumption of milk containing Lactobacillus rhamnosus GG, ATCC 53103 (LGG), has been shown to reduce caries risk in children. The aim of the present study was to examine whether short-term consumption of cheese containing LGG and Lactobacillus rhamnosus LC 705 would diminish caries-associated salivary microbial counts in young adults. Altogether, 74 18–35 year-old subjects completed this double-blinded, randomised, placebo-controlled study. During the 3 week intervention, the subjects ate 5×15 g cheese per day. Oral examinations were made before and after the study. Stimulated salivary secretion rates, buffer capacity and counts of salivary Streptococcus mutans, yeast and lactobacilli were evaluated before and after the intervention and after a 3 week post-treatment period. The results showed no statistically significant difference between the groups in Streptococcus mutans counts after the intervention, but during the post-treatment period there was a significantly greater reduction in these counts in the intervention group compared to the control group (P=0.05). However, Streptococcus mutans counts decreased in 20% (P=0.01) and yeast counts in 27% (P=0.005) of all the subjects, regardless of the intervention group. Results from logistic regression showed a trend indicating that probiotic intervention might reduce the risk of the highest level of Streptococcus mutans (OR=0.37, 95% CI 0.08–1.75, P=0.21) and salivary yeasts (OR=0.40, 0.09–1.71, P=0.22).
Researcher(s):
Meurman JH et al.
Research Unit(s):
Department of Preventive Dentistry and Cariology, University of Kuopio, Kuopio, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Title of research:
Recovery of Lactobacillus strain GG (ATCC 53103) from saliva of healthy volunteers after consumption of yoghurt prepared with the bacterium.
Scientific/Medical Publication:
Microb Ecol Health Dis 1994;7:295-298
Reference:
http://informahealthcare.com/doi/abs/10.3109/08910609409141368
Abstract/Summary:
Lactobacillus GG exerts inhibitory activity against a variety of bacterial species and it appears beneficial as a probiotic in human medicine. The bacterium does not ferment sucrose and lactose which makes it interesting with respect to dental diseases. We studied the recovery of Lactobacillus GG in the oral cavities of nine subjects who consumed yoghurt produced with the strain twice daily for 7 days. The bacterium could be recovered in the saliva samples of all subjects one week after discontinuation of the consuming of the yoghurt. In eight subjects out of nine the saliva cultures were still positive 2 wks later. Thus, Lactobacillus GG appears to be able to colonise the oral cavity, although further studies are needed in order to determine any influence on the microecology of the mouth.
Researcher(s):
Yli-Knuuttila H et al.
Research Unit(s):
Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
Title of research:
Colonization of Lactobacillus rhamnosus GG in the oral cavity.
Scientific/Medical Publication:
Oral Microbiol Immunol 2006;21:129-131
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-302X.2006.00258.x/abstract
Abstract/Summary:
Background/aims:
Lactobacillus rhamnosus GG (LGG) is one of the most widely studied probiotic bacterial strain. The benefits of LGG treatment in gastrointestinal disorders are well documented. The aim of the present study was to investigate whether LGG can be detected in the oral cavity after discontinuation of administration of a product prepared with this bacterium.
Material and methods:
56 volunteers consumed Gefilus® juice (Valio Ltd, Helsinki, Finland) containing LGG during a 14-day trial period. Saliva samples were collected and cultured onto MRS agar after a clearance period and then daily after a 2-week intervention period for as long as LGG was found. LGG-like colonies were analyzed in saliva samples, identified by characteristic colony morphology, a lactose fermentation test, and PCR with specific primers.
Results:
LGG was not able to colonize the oral cavity. It could only be temporarily detected. In one female subject, however, whose medical history revealed use of LGG in childhood, the bacterium was detected in all saliva samples taken up to 5 months. (She was excluded from the intervention trial).
Conclusion:
Permanent colonization of LGG in the oral cavity is improbable but seems possible in individual cases.
Researcher(s):
Stamatova I et al.
Research Unit(s):
Faculty of Dental Medicine, Medical University, Plovdiv, Bulgaria
Institute of Dentistry, University of Helsinki, Helsinki, Finland
Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
Title of research:
In vitro evaluation of yoghurt starter lactobacilli and Lactobacillus rhamnosus GG adhesion to saliva-coated surfaces.
Scientific/Medical Publication:
Oral Microbiol Immunol 2009;24:21
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-302X.2008.00498.x/abstract
Abstract/Summary:
Aim:
The aim of the study was to evaluate the adhesion of Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus rhamnosus strain GG to saliva-coated surfaces in vitro.
Methods:
Fifteen radiolabeled dairy L. delbrueckii subsp. bulgaricus strains and L. rhamnosus GG were tested for their ability to adhere to saliva-coated hydroxyapatite beads and polystyrene microtiter plates and the radioactivity was measured by liquid scintillation counter. The effects of lysozyme on the adhesion of lactobacilli and of pretreatment with lactobacilli on the adhesion of Streptococcus sanguinis were also assessed.
Results:
All strains tested adhered to saliva-coated surfaces but with significantly different binding frequencies. The adhesion of the L. delbrueckii subsp. bulgaricus strains remained lower in comparison to L. rhamnosus strain GG. One L. delbrueckii subsp. bulgaricus strain showed binding frequency comparable to S. sanguinis. Lysozyme pretreatment of the samples significantly increased lactobacillus adhesion to saliva-coated surfaces.
Conclusion:
The present results showed significant variations in the adhesion capacity of the Lactobacillus strains studied. Adhesion to oral surfaces is of primary importance for bacterial colonization in the mouth. Only one of the L. delbrueckii subsp. bulgaricus dairy starter culture strains investigated had a high adhesion percentage. This strain might then be considered for further investigations in the oral environment.
Researcher(s):
Pham LC et al.
Research Unit(s):
Academic Centre for Dentistry Amsterdam, Division of Conservative and Preventive Dentistry, Department of Cariology, Endodontology, Pedodontology & Oral Microbiology, University of Amsterdam and VU University Amsterdam, The Netherlands
Title of research:
Effects of Lactobacillus rhamnosus GG on saliva-derived microcosms.
Scientific/Medical Publication:
Arch Oral Biol 2011;56:136-147
Reference:
http://www.aobjournal.com/article/S0003-9969(10)00281-5/abstract
Abstract/Summary:
Objective:
The probiotic strain Lactobacillus rhamnosus GG (LGG) is shown to hamper the presence of mutans streptococci in saliva and may have positive effects on oral health. We investigated the effects of LGG on the cariogenic potential and microbial composition of saliva-derived microcosms.
Design:
Single and dual species biofilms of LGG and Streptococcus mutans, and saliva-derived microcosms with or without LGG were grown in an Active Attachment Biofilm model. The microcosms were grown on bovine dentin/enamel discs in the presence or absence of sucrose (suc+/suc−). The presence of LGG was determined by multiplex ligation-dependent probe amplification (MLPA) and real-time PCR. Mutans streptococci (MS) and total viable counts, pH of the spent medium, capacity of lactate formation and integrated mineral loss in dentin was assessed. MLPA was used for identification and relative quantification of 20 oral microorganisms in the microcosms. Principal Component Analysis was applied to MLPA data.
Results:
LGG inhibited the growth of S. mutans in dual species biofilms and did not affect the pH. LGG established in saliva-derived microcosms and reduced MS counts significantly, but did not affect pH or dentin demineralization. Simultaneous growth of the microcosms with LGG under heavy cariogenic conditions (suc+) introduced a compositional shift in the microbial community. The CFU, real-time PCR and MLPA data correlated significantly.
Conclusion:
We conclude that LGG established into and inhibited the growth of MS in complex saliva-derived biofilms, but this had no significant effect on cariogenic potential of the microcosms. This suggests that other microorganisms besides MS were responsible for increased cariogenicity of sucrose-exposed biofilms.
Researcher(s):
Hedberg M et al.
Research Unit(s):
Key Centre for Applied and Nutritional Toxicology, RMIT-University, Melbourne, Vic, Australia
Department of Biochemistry and Food Chemistry, Turku University, Turku, Finland
Title of research:
Ability of diary strains of lactic acid bacteria to bind common food carcinogen, Aflatoxin B1.
Scientific/Medical Publication:
Food Chem Toxicol 1998(36);321-6
Reference:
http://www.sciencedirect.com/science/article/pii/S0278691597001609
Abstract/Summary:
This study was conducted to examine the ability of selected dairy strains of lactic acid bacteria to remove aflatoxin B1 (AFB1) from liquid media. Both Lactobacillus rhamnosus strain GG (LBGG) and L. rhamnosus strain LC-705 (LC705) can significantly (P>0.05) remove AFB1 when compared with that by other strains of either Gram-positive or Gram-negative bacteria. Removal of AFB1 by LBGG and LC705 was a rapid process with approximately 80% AFB1 removed at 0 hr. Removal of AFB1 by these two strains was both temperature and bacterial concentration dependent.
Researcher(s):
Hedberg M et al.
Research Unit(s):
Department of Odontology, Oral Microbiology, Faculty of Medicine
Department of Odontology, Paediatric Dentistry, Faculty of Medicine, Umeå University, Umeå, Sweden
Department of Cariology and Endodontics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Title of research:
Sugar fermentation in probiotic bacteria - an in vitro study.
Scientific/Medical Publication:
Oral Microbiol Immunol 2008;23:482-485
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-302X.2008.00457.x/abstract
Abstract/Summary:
Introduction:
Food supplemented with probiotic bacteria is a rapidly growing sector of the market. The aim of the present study was to evaluate and compare the acid production of selected probiotic strains available in commercial products.
Methods:
Six Lactobacillus strains (Lactobacillus plantarum 299v and 931; Lactobacillus rhamnosus GG and LB21; Lactobacillus paracasei subsp. paracasei F19, and Lactobacillus reuteri PTA 5289) were cultivated at 37°C in an anaerobic atmosphere on Man, Rogosa, Shape (MRS) agar for 48 h or MRS broth for 16 h. After centrifugation, the cells were washed and resuspended in sterile phosphate-buffered saline and immediately subjected to a fermentation assay with 12 different carbohydrates (nine sugars and three sugar alcohols) in microtiter plates with a pH indicator. The plates were examined for color changes after 24, 48, and 72 h of incubation under aerobic and anaerobic conditions. Three scores were used: negative (pH > 6.8); weak (pH 5.2–6.8), and positive (pH < 5.2). The strains were characterized with the API 50 CH system to confirm their identity.
Results:
L. plantarum fermented all the sugars except for melibiose, raffinose, and xylitol. Both L. rhamnosus strains were generally less active although L. rhamnosus GG was slightly more active than strain LB21 in the 5% CO2 setting. The latter strain exhibited negative reactions for sucrose, maltose, arabinose, and sorbitol under anaerobic conditions. The assays with L. paracasei and L. reuteri had negative or weak reactions for all tested sugars under both aerobic and anaerobic conditions.
Conclusion:
The metabolic capacity to form acid from dietary sugars differed significantly between the various probiotic strains.
Researcher(s):
Yan F et al.
Research Unit(s):
Departments of Pediatrics and Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Departments of Pediatrics and Communicable Diseases and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, Pennsylvania, USA
Departments of Pediatrics and Biochemistry and Molecular Biology, University of Southern California and Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California, USA
Title of research:
A Lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor.
Scientific/Medical Publication:
J Biol Chem 2013;288(42) 30742-51
Reference:
http://www.jbc.org/content/288/42/30742.abstract
Abstract/Summary:
p40, a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, ameliorates intestinal injury and colitis, reduces apoptosis, and preserves barrier function by transactivation of the EGF receptor (EGFR) in intestinal epithelial cells. The aim of this study is to determine the mechanisms by which p40 transactivates the EGFR in intestinal epithelial cells. Here we show that p40-conditioned medium activates EGFR in young adult mouse colon epithelial cells and human colonic epithelial cell line, T84 cells. p40 up-regulates a disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) catalytic activity, and broad spectrum metalloproteinase inhibitors block EGFR transactivation by p40 in these two cell lines. In ADAM17-deficient mouse colonic epithelial (ADAM17−/− MCE) cells, p40 transactivation of EGFR is blocked, but can be rescued by re-expression with WT ADAM17. Furthermore, p40 stimulates release of heparin binding (HB)-EGF, but not transforming growth factor (TGF)α or amphiregulin, in young adult mouse colon cells and ADAM17−/− MCE cells overexpressing WT ADAM17. Knockdown of HB-EGF expression by siRNA suppresses p40 effects on transactivating EGFR and Akt, preventing apoptosis, and preserving tight junction function. The effects of p40 on HB-EGF release and ADAM17 activation in vivo are examined after administration of p40-containing pectin/zein hydrogel beads to mice. p40 stimulates ADAM17 activity and EGFR activation in colonic epithelial cells and increases HB-EGF levels in blood from WT mice, but not from mice with intestinal epithelial cell-specific ADAM17 deletion. Thus, these data define a mechanism of a probiotic-derived soluble protein in modulating intestinal epithelial cell homeostasis through ADAM17-mediated HB-EGF release, leading to transactivation of EGFR.
Researcher(s):
Orlando A et al.
Research Unit(s):
Laboratory of Nutritional Pathophysiology, National Institute for Digestive Diseases I.R.C.C.S. “Saverio de Bellis”, via Turi 27, I-70013 Castellana Grotte, BA, Italy
Laboratory of Nutritional Biochemistry, National Institute for Digestive Diseases I.R.C.C.S. “Saverio de Bellis”, via Turi 27, I-70013 Castellana Grotte, BA, Italy
Title of research:
Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption the role of cellular polyamines.
Scientific/Medical Publication:
BMC Microbiology 2014;14:19
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911798/
Abstract/Summary:
Background:
Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. Polyamines are pivotal in the control of intestinal barrier function and are also involved in the regulation of intercellular junction proteins. Different probiotic strains may inhibit gliadin-induced toxic effects and the Lactobacillus rhamnosus GG (L.GG) is effective in the prevention and treatment of gastrointestinal diseases. Aims of the study were to establish in epithelial Caco-2 cells whether i) gliadin affects paracellular permeability and polyamine profile; ii) co-administration of viable L.GG, heat-killed L.GG (L.GG-HK) or its conditioned medium (L.GG-CM) preserves the intestinal epithelial barrier integrity. Additionally, the effects of L.GG on TJ protein expression were tested in presence or absence of polyamines.
Results:
Administration of gliadin (1 mg/ml) to Caco-2 cells for 6 h caused a significant alteration of paracellular permeability as demonstrated by the rapid decrease in transepithelial resistance with a concomitant zonulin release. These events were followed by a significant increase in lactulose paracellular transport and a slight lowering in ZO-1 and Occludin expression without affecting Claudin-1. Besides, the single and total polyamine content increased significantly. The co-administration of viable L.GG (108 CFU/ml), L.GG-HK and L.GG-CM with gliadin significantly restored barrier function as demonstrated by transepithelial resistance, lactulose flux and zonulin release. Viable L.GG and L.GG-HK, but not L.GG-CM, led to a significant reduction in the single and total polyamine levels. Additionally, only the co-administration of viable L.GG with gliadin significantly increased ZO-1, Claudin-1 and Occludin gene expression compared to control cells. When Caco-2 cells treated with viable L.GG and gliadin were deprived in the polyamine content by α-Difluoromethylornithine, the expression of TJ protein mRNAs was not significantly different from that in controls or cells treated with gliadin alone.
Conclusions:
Gliadin modifies the intestinal paracellular permeability and significantly increases the polyamine content in Caco-2 cells. Concomitant administration of L.GG is able to counteract these effects. Interestingly, the presence of cellular polyamines is necessary for this probiotic to exert its capability in restoring paracellular permeability by affecting the expression of different TJ proteins.
Researcher(s):
Horvath A et al.
Research Unit(s):
Department of Paediatrics, The Medical University of Warsaw, Poland.
Title of research:
Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2011;33:1302-10
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04665.x/full
Abstract/Summary:
Background:
A lack of reliable treatments for abdominal pain-related functional gastrointestinal disorders prompts interest in new therapies.
Aim:
To evaluate systematically the effect of Lactobacillus rhamnosus GG (LGG) for treating abdominal pain-related functional gastrointestinal disorders in children.
Methods:
MEDLINE, EMBASE, CINAHL, the Cochrane Library, trial registries and proceedings of major meetings were searched for randomised controlled trials (RCTs) evaluating LGG supplementation in children with abdominal pain-related functional gastrointestinal disorders based on the Rome II or Rome III criteria. Risk of bias was assessed for generation of the allocation sequence, allocation concealment, blinding and follow-up.
Results:
Compared with placebo, LGG supplementation was associated with a significantly higher rate of treatment responders (defined as no pain or a decrease in pain intensity) in the overall population with abdominal pain-related functional gastrointestinal disorders (three RCTs, n = 290; risk ratio, RR 1.31, 95% CI 1.08–1.59, number needed to treat, NNT 7, 95% CI 4–22) and in the irritable bowel syndrome (IBS) subgroup (three RCTs, n = 167; RR 1.70, 95% CI 1.27–2.27, NNT 4, 95% CI 3–8). However, no difference was found in the rate of treatment responders between children with functional abdominal pain or functional dyspepsia who received placebo or LGG. The intensity of pain was significantly reduced in the overall study population and in the IBS subgroup. The frequency of pain was significantly reduced in the IBS subgroup only.
Conclusion:
The use of Lactobacillus rhamnosus GG moderately increases treatment success in children with abdominal pain-related functional gastrointestinal disorders, particularly among children with IBS.
Researcher(s):
Tao Y et al.
Research Unit(s):
Section of Infectious Diseases, Department of Medicine, University of Chicago, Chicago, Illinois
Martin Boyer and IBD Research Center, University of Chicago, Chicago, Illinois
Department of Surgery, University of Chicago, Chicago, Illinois
Department of Microbiology, University of Chicago, Chicago, Illinois
Title of research:
Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells.
Scientific/Medical Publication:
Am J Physiol Cell Physiol 2006;290:C1018-30
Reference:
http://ajpcell.physiology.org/content/290/4/C1018
Abstract/Summary:
Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce heat shock protein (Hsp) expression in intestinal epithelial cells. LGG-CM induces both Hsp25 and Hsp72 in a time- and concentration-dependent manner. These effects are mediated by a low-molecular-weight peptide that is acid and heat stable. DNA microarray experiments demonstrate that Hsp72 is one of the most highly upregulated genes in response to LGG-CM treatment. Real-time PCR and electrophoretic mobility shift assay confirm that regulation of Hsp induction is at least in part transcriptional in nature, involving heat shock factor-1. Although Hsps are not induced for hours after exposure, transient exposure to LGG-CM is sufficient to initiate the signal for Hsp induction, suggesting that signal transduction pathways may be involved. Experiments confirm that LGG-CM modulates the activity of certain signaling pathways in intestinal epithelial cells by activating MAP kinases. Inhibitors of p38 and JNK block the expression of Hsp72 normally induced by LGG-CM. Functional studies indicate that LGG-CM treatment of gut epithelial cells protects them from oxidant stress, perhaps by preserving cytoskeletal integrity. By inducing the expression of cytoprotective Hsps in gut epithelial cells, and by activating signal transduction pathways, the peptide product(s) secreted by LGG may contribute to the beneficial clinical effects attributed to this probiotic.
Researcher(s):
Donato KA et al.
Research Unit(s):
Cell Biology Program, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Title of research:
Lactobacillus rhamnosus GG attenuates interferon-ɣ and tumor necrosis factor-ɑ-induced barrier dysfunction and pro-inflammatory signalling.
Scientific/Medical Publication:
Microbiology 2010 July 23;doi:10.1099/mic.0.040139-0
Reference:
http://mic.sgmjournals.org/content/156/11/3288.long
Abstract/Summary:
The intestinal epithelium forms a protective barrier against luminal contents and the external environment, mediated via intercellular tight junctions (TJs). The TJ can be disrupted via cell signalling induced by either enteric pathogens or pro-inflammatory cytokines, thereby contributing to various intestinal disorders ranging from acute infectious diarrhoea to chronic inflammatory bowel diseases. Probiotics, such as Lactobacillus rhamnosus GG (LGG), are reported to confer beneficial effects on epithelial cells, including antagonizing infections and reducing overt pro-inflammatory responses, but the underlying mechanisms of these observed effects require further characterization. We hypothesized that probiotics preserve barrier function by interfering with pro-inflammatory cytokine signalling. Caco-2bbe cells were seeded into Transwells to attain polarized monolayers with intercellular TJs. Monolayers were inoculated apically with the probiotic LGG 3 h prior to the addition of IFN-γ (100 ng ml−1) to the basolateral medium overnight. The monolayers were then placed in fresh basal medium±TNF-α (10 ng ml−1) and transepithelial electrical resistance (TER) measurements were taken over the time-course of TNF-α stimulation. To complement the TER findings, cells were processed for zona occludens-1 (ZO-1) immunofluorescence staining. As a measure of TNF-α downstream signalling, cells were immunofluorescently stained for NF-κB p65 subunit and CXCL-8 mRNA was quantified by qRT-PCR. Basal cell culture medium was collected after overnight TNF-α stimulation to measure secreted chemokines, including CXCL-8 (interleukin-8) and CCL-11 (eotaxin). Following LGG inoculation, IFN-γ priming and 24 h TNF-α stimulation, epithelial cells maintained TER and ZO-1 distribution. LGG diminished the nuclear translocation of p65, demonstrated by both immunofluorescence and CXCL-8 mRNA expression. CXCL-8 and CCL-11 protein levels were decreased in LGG-inoculated, cytokine-challenged cells. These findings indicate that LGG alleviates the effects of pro-inflammatory cytokines on epithelial barrier integrity and inflammation, mediated, at least in part, through inhibition of NF-κB signalling.
Researcher(s):
Lam EKY et al.
Research Unit(s):
Department of Pharmacology, The University of Hong Kong, China
Department of Pharmacology, Faculty of Medicine, Basic Medical Sciences Building, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Department of Microbiology, The University of Hong Kong, China
Title of research:
Enhancement of gastric mucosal integrity by Lactobacillus rhamnosus GG.
Scientific/Medical Publication:
Life Sciences 2007;80:2128-36
Reference:
http://www.sciencedirect.com/science/article/pii/S0024320507002822?via=ihub
Abstract/Summary:
The gastric mucosa is frequently exposed to different exogenous and endogenous ulcerative agents. Alcoholism is one of the risk factors for the development of mucosal damage in the stomach. This study aimed to assess if a probiotic strain Lactobacillus rhamnosus GG (LGG) is capable of protecting the gastric mucosa from acute damage induced by intragastric administration of ethanol. Pre-treatment of rats with LGG at 109 cfu/ml twice daily for three consecutive days markedly reduced ethanol-induced mucosal lesion area by 45%. LGG pre-treatment also significantly increased the basal mucosal prostaglandin E2 (PGE2) level. In addition, LGG attenuated the suppressive actions of ethanol on mucus-secreting layer and transmucosal resistance and reduced cellular apoptosis in the gastric mucosa. It is suggested that the protective action of LGG on ethanol-induced gastric mucosal lesions is likely attributed to the up-regulation of PGE2, which could stimulate the mucus secretion and increase the transmucosal resistance in the gastric mucosa. All these would protect mucosal cells from apoptosis in the stomach.
Researcher(s):
Lam EKY et al.
Research Unit(s):
Department of Pharmacology, The University of Hong Kong, China
Department of Pharmacology, The Chinese University of Hong Kong, HKSAR, China
Department of Microbiology, The University of Hong Kong, China
Title of research:
Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats.
Scientific/Medical Publication:
Eur J Pharmacol 2007;565:171-179
Reference:
http://www.sciencedirect.com/science/article/pii/S0014299907002543
Abstract/Summary:
Probiotics are widely used as functional foods which have been advocated for the maintenance of gastrointestinal microflora equilibrium and treatment of gastrointestinal disorders. However, studying the role of probiotics in peptic ulcer disease is limited. The aim of the present study is to investigate the effect of a probiotic strain Lactobacillus rhamnosus GG on gastric ulcer and to elucidate the mechanisms involved. Gastric kissing ulcers were induced in rats by acetic acid (60% v/v). L. rhamnosus GG was given intragastrically at 108 cfu/day or 109 cfu/day for three consecutive days after ulcer induction. L. rhamnosus GG successfully colonized in the gastric mucosa especially at the ulcer margin. It also significantly and dose-dependently reduced gastric ulcer area. Cell apoptosis to cell proliferation ratio was strongly decreased and accompanied by significant up-regulation of ornithine decarboxylase (ODC) and B-cell lymphoma 2 (Bcl-2) protein expression at the ulcer margin. Angiogenesis was also significantly stimulated together with the induction of vascular endothelial growth factor (VEGF) expression. Furthermore, L. rhamnosus GG up-regulated the phosphorylation level of epidermal growth factor receptor (EGF receptor) without altering the total EGF receptor expression. These findings suggested that L. rhamnosus GG enhanced gastric ulcer healing via the attenuation of cell apoptosis to cell proliferation ratio and increase in angiogenesis. Regulators of these processes such as ODC, Bcl-2, VEGF and EGF receptor are likely to be involved in the healing action of L. rhamnosus GG for gastric ulcer.
Researcher(s):
Sultana R et al.
Research Unit(s):
Schools of Medicine, The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
Title of research:
Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates.
Scientific/Medical Publication:
Appl Environ Microbiol 2013;79(16):4887-4894
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754719/
Abstract/Summary:
In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the exception of L. fermentum (which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However, B. longum and L. rhamnosus GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by B. longum, but not L. rhamnosus GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.
Researcher(s):
Sindhu KNC et al.
Research Unit(s):
Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Department of Public Health and Community Medicine, Tufts University School of Medicine
Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
Title of research:
Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: A randomized, double-blind, placebo-controlled trial.
Scientific/Medical Publication:
Clin Infect Dis 2014;58(8):1107-15.
Reference:
http://cid.oxfordjournals.org/content/58/8/1107.abstract
Abstract/Summary:
Background:
Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea.
Methods:
Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up.
Results:
Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability.
Conclusions:
LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection.
Researcher(s):
Gotteland M et al.
Research Unit(s):
Gastroenterology Unit, Institute of Nutrition and Food Technology (INTA), University of Chile, Chile
Title of research:
Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alteration induced by indometacin in humans.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2001;15:11-17
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2001.00898.x/abstract
Abstract/Summary:
Background:
Chronic nonsteroidal anti-inflammatory drug (NSAID) ingestion strongly affects the gastrointestinal mucosa as a first stage before ulceration. Some Lactobacillus strains may stabilize the mucosal barrier by increasing mucin expression, reducing bacterial overgrowth, stimulating mucosal immunity and synthetizing antioxidant substances; these events are altered in NSAID-associated gastroenteropathy.
Aim:
To determine whether ingestion of the probiotic Lactobacillus GG (LGG) protects the gastrointestinal mucosa against indometacin-induced alterations of permeability.
Subjects and methods:
Four gastrointestinal permeability tests were carried out in random order in 16 healthy volunteers: (i) basal; (ii) after indometacin; (iii) after 5 days of living LGG ingestion before indometacin administration; (iv) after 5 days of heat-killed LGG ingestion before indometacin administration.
Results:
Indometacin significantly increased basal sucrose urinary excretion (29.6 mg [17.1–42.1] vs. 108.5 mg [68.2–148.7], P=0.0030) (means [95% CI]) and lactulose/mannitol urinary excretion (1.03% [0.73–1.32] vs. 2.93% [1.96–3.90], P=0.00012). Heat-killed LGG did not modify the indometacin-induced increase of gastrointestinal permeability, while live bacteria significantly reduced the alteration of gastric (47.8 mg [31.1–64.6], P=0.012) but not intestinal permeability induced by NSAID.
Conclusions:
Regular ingestion of LGG protects the integrity of the gastric mucosal barrier against indometacin, but has no effect at the intestinal level.
Researcher(s):
Francavilla R et al.
Research Unit(s):
Departments of Developmental Biomedicine, University of Bari, Bari, Italy
Emergency and Organ Transplantation, Gastroenterology Section, University of Bari, Bari, Italy
Department of Pediatrics, University of Catania, Catania, Italy
Department of Pediatrics, San Paolo Hospital, Bari, Italy
ASL-Bari, Bari, Italy
Title of research:
A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain.
Scientific/Medical Publication:
Pediatrics 2010,126:e1445-1452
Reference:
http://pediatrics.aappublications.org/content/126/6/e1445.long
Abstract/Summary:
Objective:
Our aim was to determine whether Lactobacillus rhamnosus GG (LGG) relieves symptoms in children with recurrent abdominal pain.
Patients and methods:
A total of 141 children with irritable bowel syndrome (IBS) or functional pain were enrolled in 9 primary care sites and a referral center. Children entered a randomized, double-blind, placebo-controlled trial and received LGG or placebo for 8 weeks and entered follow-up for 8 weeks. The primary outcome was overall pain at the end of the intervention period. At entry and at the end of the trial, children underwent a double-sugar intestinal permeability test.
Results:
Compared with baseline, LGG, but not placebo, caused a significant reduction of both frequency (P < .01) and severity (P < .01) of abdominal pain. These differences still were significant at the end of follow-up (P < .02 and P < .001, respectively). At week 12, treatment success was achieved in 48 children in the LGG group compared with 37 children in the placebo group (P < .03); this difference still was present at the end of follow-up (P < .03). At entry, 59% of the children had abnormal results from the intestinal permeability test; LGG, but not placebo, determined a significant decrease in the number of patients with abnormal results from the intestinal permeability testing (P < .03). These effects mainly were in children with IBS.
Conclusions:
LGG significantly reduces the frequency and severity of abdominal pain in children with IBS; this effect is sustained and may be secondary to improvement of the gut barrier.
Researcher(s):
Di Caro S et al.
Research Unit(s):
Department of Gastroenterology, Catholic University of Rome, Largo Gemelli 1, 00168 Rome, Italy
Department of Pathology, University of Pittsburgh Medical Centre, PA, USA
Title of research:
Effects of Lactobacillus GG on genes expression pattern in a small bowel mucosa.
Scientific/Medical Publication:
Dig Liver Dis 2005;37:320-329
Reference:
http://www.sciencedirect.com/science/article/pii/S1590865805000095
Abstract/Summary:
Background and aims:
Probiotics have been used for cure and prevention of several clinical conditions. However, further insights into the mechanism of action are needed to understand the rationale of their use. The aim of this study was to investigate the influence of Lactobacillus GG on the genetic expression patterns in the small bowel mucosa.
Methods:
Six male patients (38 ± 5 years) with endoscopically proven oesophagitis were enrolled. All patients were treated for 1 month with esomeprazole and randomised to receive Lactobacillus GG or placebo. After 1 month of treatment, upper endoscopy was repeated. Biopsies of the duodenal mucosa were taken prior to and after the treatment, and the genes expression patterns were assessed using GeneChip Human U133A array. Genes with significant expression changes were selected and analysed to identify specific cellular pathways modified by Lactobacillus GG. To support the array data, 10 target genes were studied using Syber-Green PCR.
Results:
Microarray analysis showed that Lactobacillus GG administration determined the up- and down-regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the reliability of the analysis. Lactobacillus GG mainly affected the expression of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell growth and cell differentiation (cyclins and caspases, oncogenes), cell–cell signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription and transduction.
Conclusions:
These data indicate that administration of Lactobacillus GG is associated with a complex genetic response of the duodenal mucosa, reflected by the up- and down-regulation of several genes involved in specific cellular pathways.
Researcher(s):
Commane DM et al.
Research Unit(s):
NICHE, The University of Ulster, Coleraine, Northern Ireland.
Dipartimento Scienze Morfologiche e Biochimiche Comparate, Universita degli Studi di Camerino, Italy
Yakult UK Ltd, London, England
Title of research:
Effects of fermentation products of pro-and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon.
Scientific/Medical Publication:
Nutr Cancer 2005:51:102-109
Reference:
Abstract/Summary:
Evidence from in vivo and in vitro studies suggests that the consumption of pro- and prebiotics may inhibit colon carcinogenesis; however, the mechanisms involved have, thus far, proved elusive. There are some indications from animal studies that the effects are being exerted during the promotion stage of carcinogenesis. One feature of the promotion stage of colorectal cancer is the disruption of tight junctions, leading to a loss of integrity across the intestinal barrier. We have used the Caco-2 human adenocarcinoma cell line as a model for the intestinal epithelia. Trans-epithelial electrical resistance measurements indicate Caco-2 monolayer integrity, and we recorded changes to this integrity following exposure to the fermentation products of selected probiotics and prebiotics, in the form of nondigestible oligosaccharides (NDOs). Our results indicate that NDOs themselves exert varying, but generally minor, effects upon the strength of the tight junctions, whereas the fermentation products of probiotics and NDOs tend to raise tight junction integrity above that of the controls. This effect was bacterial species and oligosaccharide specific. Bifidobacterium Bb 12 was particularly effective, as were the fermentation products of Raftiline and Raftilose. We further investigated the ability of Raftilose fermentations to protect against the negative effects of deoxycholic acid (DCA) upon tight junction integrity. We found protection to be species dependent and dependent upon the presence of the fermentation products in the media at the same time as or after exposure to the DCA. Results suggest that the Raftilose fermentation products may prevent disruption of the intestinal epithelial barrier function during damage by tumor promoters.
Researcher(s):
Kajander K et al.
Research Unit(s):
Valio Ltd, Research Centre, Helsinki
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki
Stat-Consulting, Tampere
Department of Gastroenterology, Helsinki University Central Hospital, Helsinki
Foundation for Nutrition Research, Helsinki, Finland
Title of research:
A Probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention.
Scientific/Medical Publication:
Aliment Pharmacol Ther 2005;22:387-394
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02579.x/abstract
Abstract/Summary:
Background :
Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology. The effect of probiotics in this syndrome remains unclear.
Aim :
To investigate whether a probiotic mixture containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS is effective in alleviating irritable bowel syndrome symptoms.
Methods :
A total of 103 patients fulfilling the Rome I or II criteria took part in this 6-month, randomized, double-blind placebo-controlled trial. The patients received a probiotic capsule or a placebo capsule daily. Gastrointestinal symptoms and bowel habits were recorded.
Results :
At the end the total symptom score (abdominal pain + distension + flatulence + borborygmi) was 7.7 (95% CI: −13.9 to −1.6) points lower in the probiotic group (P = 0.015). This represents a median reduction of 42% in the symptom score of the probiotic group compared with 6% in the placebo group. In individual symptoms, borborygmi was milder in the probiotic group (P = 0.008), and for the rest of the symptoms there was a non-significant trend.
Conclusions :
The results indicate that this probiotic mixture is effective in alleviating irritable bowel syndrome symptoms. Considering the high prevalence of irritable bowel syndrome and the lack of effective therapies, even a slight reduction in symptoms could have positive public health consequences.
Researcher(s):
Lyra A et al.
Research Unit(s):
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
Valio Ltd., Research Centre, Helsinki, Finland
Numos Ltd., Espoo, Finland
Institute of Biomedicine, University of Helsinki, Helsinki, Finland
Title of research:
Effect of a multispecies probiotic supplement on quantity of irritable bowel syndrome-related intestinal microbial phylotypes.
Scientific/Medical Publication:
BMC Gastroenterol 2010;1-10
Reference:
http://www.biomedcentral.com/1471-230X/10/110
Abstract/Summary:
Background:
Probiotics can alleviate the symptoms of irritable bowel syndrome (IBS), possibly by stabilizing the intestinal microbiota. Our aim was to determine whether IBS-associated bacterial alterations were reduced during multispecies probiotic intervention consisting of Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. The intervention has previously been shown to successfully alleviate gastrointestinal symptoms of IBS.
Methods:
The faecal microbiotas of 42 IBS subjects participating in a placebo-controlled double-blind multispecies probiotic intervention were analysed using quantitative real-time polymerase chain reaction (qPCR). Eight bacterial targets within the gastrointestinal microbiota with a putative IBS association were measured.
Results:
A phylotype with 94% similarity to Ruminococcus torques remained abundant in the placebo group, but was decreased in the probiotic group during the intervention (P = 0.02 at 6 months). In addition, the clostridial phylotype, Clostridium thermosuccinogenes 85%, was stably elevated during the intervention (P = 0.00 and P = 0.02 at 3 and 6 months, respectively). The bacterial alterations detected were in accordance with previously discovered alleviation of symptoms.
Conclusions:
The probiotic supplement was thus shown to exert specific alterations in the IBS-associated microbiota towards the bacterial 16S rDNA phylotype quantities described previously for subjects free of IBS. These changes may have value as non-invasive biomarkers in probiotic intervention studies.
Researcher(s):
Hongisto S-M et al.
Research Unit(s):
Valio Ltd, R&D, Helsinki, Finland
Foundation for Nutrition Research, Helsinki, Finland
Department of Allergy, Helsinki University Central Hospital, Helsinki, Finland
Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
Title of research:
A combination of fibre-rich rye bread and yoghurt containing Lactobacillus GG improves bowel function in women with self-reported constipation.
Scientific/Medical Publication:
Eur J Clin Nutr 2006;60(3):319-324
Reference:
http://www.nature.com/ejcn/journal/v60/n3/full/1602317a.html
Abstract/Summary:
Objective:
The aim of the study was to investigate the effects of fibre-rich rye bread and yoghurt containing Lactobacillus GG (LGG) on intestinal transit time and bowel function, and to test whether they have an interaction in cases of self-reported constipation.
Design:
The study was carried out as a two-by-two factorial design.
Setting:
Free-living subjects.
Subjects:
A total of 59 healthy women with self-reported constipation, recruited by advertisement.
Interventions: After a baseline period, the subjects were randomized into four diet groups: (1) rye bread+LGG yoghurt, (2) rye bread, (3) LGG yoghurt, and (4) control. The 3-week dietary intervention was followed by a 3-week follow-up period. During each period, total intestinal transit time was measured and the subjects recorded faecal frequency and consistency, difficulty in defecation and gastrointestinal symptoms.
Results:
The rye bread shortened total intestinal transit time (mean difference, -0.7; CI95, -1.1 to -0.2; P=0.007), increased faecal frequency (0.3; CI95, 0.1 to 0.5; P=0.001), softened faeces (-0.3; CI95, -0.4 to -0.2; P<0.001) and made defecation easier (-0.4; CI95, -0.5 to -0.2; P<0.001), but also increased gastrointestinal symptoms (1.6; CI95, 0.7 to 2.4; P<0.001) compared to the low-fibre toast consumed in the LGG and control groups. There were fewer symptoms in the rye bread+LGG group compared to the rye bread group (-1.3; CI95, -2.4 to -0.2; P=0.027).
Conclusions:
Fibre-rich rye bread can be recommended in the treatment of constipation, and the simultaneous consumption of LGG yoghurt relieves the adverse gastrointestinal effects associated with increased intake of fibre.
Researcher(s):
Guarino MP et al.
Research Unit(s):
Department of Digestive Diseases, Campus Biomedico University, Via Alvaro del Portillo, Rome, Italy.
Title of research:
Effect of acute mucosal exposure to Lactobacillus rhamnosus GG on human colonic smooth muscle cells.
Scientific/Medical Publication:
J Clin Gastroentorol 2008;42(Suppl 3) Pt 2:S185-190
Reference:
Abstract/Summary:
Aim:
To define whether human colonic mucosa exposure to Lactobacillus rhamnosus GG (LGG), American Type Culture Collection (ATCC) 53103, may influence intestinal muscle cell contractility.
Methods:
Human colon specimens were obtained from disease-free margins of resected segments for cancer. The mucosa and submucosa, after dissection, were sealed between 2 chambers, with the luminal side of the mucosa facing upward and covered with 5 mL of Krebs solution and the submucosal side facing downward into 20 mL of Krebs solution. LGG or normal undernatant (N-undernatant) were added to the luminal side of the mucosa for 30 minutes. Smooth muscle cells (SMCs), isolated from the circular muscle layer, were exposed to undernatant for 30 minutes from the submucosal chamber of mucosa that was either preexposed to N-undernatant or to LGG (36×109 colony forming units/mL) (LGG-undernatant). Acetylcholine (Ach) dose-response was obtained for SMCs.
Results:
SMCs exposed to N-undernatant presented a dose-response to Ach (maximal contraction: 32%±5% with 1-μM Ach) that is similar to unstimulated SMCs. Exposure to LGG-undernatant resulted both in an 18%±3% cell shortening and a 78%±7% inhibition of maximal Ach-induced contraction. When SMCs were directly exposed to LGG, a significant impairment of contraction (70%±5%, compared with control cells) and a dose-dependent and time-dependent shortening were observed.
Conclusions:
After acute exposure of colonic mucosa to LGG, a significant shortening of SMCs is observed that possibly contributes to the reduced contractile response to Ach. Further studies are needed to establish the mechanisms of this effect that could account for the clinical efficacy of probiotics in intestinal disorders.
Researcher(s):
Bruzzese E et al.
Research Unit(s):
Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy
Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy
Charité-University Medicine Berlin, Germany
Title of research:
Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and Its Restoration with Lactobacillus GG — A Randomised Clinical Trial.
Scientific/Medical Publication:
PLoS One, 2014;9(2):e87796
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929570/
Abstract/Summary:
Background & Aims:
Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment.
Methods:
The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG.
Results:
Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2–9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2−, respectively; P<0.01). Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation.
Conclusions:
CF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota, supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations.
Researcher(s):
Nanji AA et al.
Research Unit(s):
Harvard Medical School, Boston, Massachusetts 02215, USA
Department of Pathology, New England Deaconess Hospital,Boston, Massachusetts 02215, USA
Title of research:
Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease).
Scientific/Medical Publication:
Proc Soc Exp Biol Med 1994;205(3):243-247
Reference:
http://ebm.sagepub.com/content/205/3/243.short
Abstract/Summary:
We have previously shown a relationship between plasma endotoxin levels and severity of alcoholic liver injury in the intragastric feeding rat model. We attempted to reduce both circulating endotoxin and liver injury in this model by administering a lactobacillus strain (species GG) which survives for prolonged periods in the gastrointestinal tract. Male Wistar rats were fed ethanol and liquid diet containing corn oil (CO + E). Another group of animals (CO + E + L) received the diet containing ethanol plus a daily bolus of lactobacilli GG concentrate (1010 CFU). All animals were sacrificed after one month. All animals had plasma endotoxin measurements and evaluation of severity of pathologic changes in the liver. The weight gain and blood alcohol levels were similar in both groups. The mean ± SE of the pathology score was significantly higher (3.4 ± 0.85) in the CO + E group compared to the CO + E + L group (0.5 ± 0.3, P < 0.01). The virtual absence of pathologic changes in the latter group was accompanied by significantly lower endotoxin levels (8.4 ± 2.9 pg/ml in CO + E + L group vs 48.3 ± 7.8 pg/ml in CO + E group, P < 0.01). Feeding of strains of lactobacilli that survive in the gastrointestinal tract reduces endotoxemia and alcohol-induced liver injury in the rat. Lactobacillus species GG provides a potential nontoxic form of therapy for both endotoxemia and alcoholic liver disease.
Researcher(s):
Wang Y et al.
Research Unit(s):
Department of Medicine, University of Louisville School of Medicine, Louisville, KY
College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
School of Pharmacy, Wenzhou Medical College, Wenzhou, China
Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY
First Hospital, Xi’an Jiaotong University, Xi'an, China
College of Life Sciences, Northwest University, Xi'an, China
College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY
Robley Rex Veterans Affairs Medical Center, Louisville, KY
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY
Title of research:
Lactobacillus rhamnosus GG reduces hepatic TNF-α production and inflammation in chronic alcohol-induced liver injury.
Scientific/Medical Publication:
J Nutr Biochem 2013;24:1609-1615
Reference:
http://www.jnutbio.com/article/S0955-2863(13)00039-9/abstract
Abstract/Summary:
The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8 weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose-dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4- and TLR5-mediated endotoxin activation.
Researcher(s):
Nosova T.
Research Unit(s):
Research Unit of Alcohol Diseases, University Central Hospital of Helsinki and
Anaerobe Reference Laboratory, National Public Health Institute, Helsinki, Finland
Title of research:
Acetaldehyde production and metabolism by human indigenous and probiotic Lactobacillus and Bifidobacterium strains.
Scientific/Medical Publication:
Alcohol Alcohol 2000;35(6):561-568
Reference:
http://alcalc.oxfordjournals.org/content/35/6/561.long
Abstract/Summary:
Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to acetaldehyde. We examined whether human gastrointestinal lactobacilli (three strains), bifidobacteria (five strains) and probiotic Lactobacillus GG ATCC 53103 are also able to metabolize ethanol and acetaldehyde in vitro. Acetaldehyde production by bacterial suspensions was determined by gas chromatography after a 1-h incubation with 22 mM ethanol. To determine the acetaldehyde consumption, the suspensions were incubated with 50 μM or 500 μM acetaldehyde as well as with 500 μM acetaldehyde and 22 mM ethanol, i.e. under conditions resembling those in the human colon after alcohol intake. The influence of growth media and bacterial concentration on the ability of lactobacilli to metabolize acetaldehyde and to produce acetate from acetaldehyde were determined. ADH and aldehyde dehydrogenase (ALDH) activities were determined spectrophotometrically. Neither measurable ADH nor ALDH activities were found in aerobically grown Lactobacillus GG ATCC 53103 and Lactobacillus acidophilus ATCC 4356 strains. All the lactobacilli and bifidobacteria strains revealed a very limited capacity to oxidize ethanol to acetaldehyde in vitro. Lactobacillus GG ATCC 53103 had the highest acetaldehyde-metabolizing capacity, which increased significantly with increasing bacterial concentrations. This was associated with a marked production of acetate from acetaldehyde. The type of the growth media had no effect on acetaldehyde consumption. Addition of ethanol to the incubation media diminished the acetaldehyde-metabolizing capacity of all strains. However, in the presence of ethanol, Lactobacillus GG ATCC 53103 still demonstrated the highest capacity for acetaldehyde metabolism of all strains. These data suggest a beneficial impact of Lactobacillus GG ATCC 53103 on high gastrointestinal acetaldehyde levels following alcohol intake. The possible clinical implications of this finding remain to be established in in vitro studies.
Researcher(s):
Wang Y et al.
Research Unit(s):
College of Food Science and Engineering,Jilin Agricultural University, Changchun, China
Departments of Medicine and Pharmacology and Toxicology and the Alcohol Research Center,University of Louisville, Louisville, Kentucky
School of Pharmacy,Wenzhou Medical College, Zhejiang, China
First Hospital, Xi’an Jiaotong University, Shaanxi, China
Robby Rex Veterans Affairs Medical Center,Louisville, Kentucky
Title of research:
Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury.
Scientific/Medical Publication:
Am J Pathol 2011;179:2866-2875
Reference:
http://www.journals.elsevierhealth.com/periodicals/ajpa/article/S0002-9440(11)00858-3/abstract
Abstract/Summary:
Gut-derived endotoxin is a critical factor in the development and progression of alcoholic liver disease (ALD). Probiotics can treat alcohol-induced liver injury associated with gut leakiness and endotoxemia in animal models, as well as in human ALD; however, the mechanism or mechanisms of their beneficial action are not well defined. We hypothesized that alcohol impairs the adaptive response-induced hypoxia-inducible factor (HIF) and that probiotic supplementation could attenuate this impairment, restoring barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. C57BJ/6N mice were fed the Lieber DeCarli diet containing 5% alcohol for 8 weeks. Animals received Lactobacillus rhamnosus GG (LGG) supplementation in the last 2 weeks. LGG supplementation significantly reduced alcohol-induced endotoxemia and hepatic steatosis and improved liver function. LGG restored alcohol-induced reduction of HIF-2α and intestinal trefoil factor levels. In vitro studies using the Caco-2 cell culture model showed that the addition of LGG supernatant prevented alcohol-induced epithelial monolayer barrier dysfunction. Furthermore, gene silencing of HIF-1α/2α abolished the LGG effects, indicating that the protective effect of LGG is HIF-dependent. The present study provides a mechanistic insight for utilization of probiotics for the treatment of ALD, and suggests a critical role for intestinal hypoxia and decreased trefoil factor in the development of ALD.
Researcher(s):
Zhu L et al.
Research Unit(s):
Digestive Diseases and Nutrition Center, Department of Pediatrics, the State University of New York at Buffalo, Buffalo, NY
Department of Microbiology and Immunology, University of Rochester, Rochester, NY
Title of research:
Characterization of the gut microbiome in non-alcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH.
Scientific/Medical Publication:
Hepatology 2013;57:601– 609.
Reference:
Abstract/Summary:
Nonalcoholic steatohepatitis (NASH) is a serious liver disease associated with obesity. Characterized by metabolic syndrome, hepatic steatosis, and liver inflammation, NASH is believed to be under the influence of the gut microflora. Here, the composition of gut bacterial communities of NASH, obese, and healthy children was determined by 16S ribosomal RNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of patients and healthy controls. UniFrac-based principle coordinates analysis indicated that most of the microbiome samples clustered by disease status. Each group was associated with a unique pattern of enterotypes. Differences were abundant at phylum, family, and genus levels between healthy subjects and obese patients (with or without NASH), and relatively fewer differences were observed between obese and the NASH microbiomes. Among those taxa with greater than 1% representation in any of the disease groups, Proteobacteria, Enterobacteriaceae, and Escherichia were the only phylum, family and genus types exhibiting significant difference between obese and NASH microbiomes. Similar blood-ethanol concentrations were observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol levels. Conclusions: The increased abundance of alcohol-producing bacteria in NASH microbiomes, elevated blood-ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and, consequently, liver inflammation suggest a role for alcohol-producing microbiota in the pathogenesis of NASH. We postulate that the distinct composition of the gut microbiome among NASH, obese, and healthy controls could offer a target for intervention or a marker for disease.
Researcher(s):
Kirpich IA et al.
Research Unit(s):
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, KY 40202, USA.
Title of research:
Probiotics in the treatment of liver disease.
Scientific/Medical Publication:
J Am Coll Nutr 2012;31(1):14-13
Reference:
http://www.tandfonline.com/doi/abs/10.1080/.VBiDg0uRBIc
Abstract/Summary:
The concept that interactions between the gut, the liver, and the immune system play an important role in liver diseases is an old concept that has recently seen a resurgence in interest. Altered intestinal bacterial flora and gut-associated endotoxemia are increasingly recognized as critical components in both nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Probiotics have been proposed in the treatment and prevention of many conditions, including the liver diseases. Probiotics are live microorganisms that, when consumed in adequate amounts, confer a health benefit to the host. There are many mechanisms by which probiotics enhance intestinal health and influence the gut-liver axis, including modulation of the intestinal microflora, modification of intestinal barrier function, and immunomodulation. The present review summarizes the recent studies highlighting the role of the intestinal microflora in the development of NAFLD and ALD and the potential efficacy of probiotics as a therapeutic strategy for liver diseases.
Researcher(s):
Yan F et al.
Research Unit(s):
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
Title of research:
Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth.
Scientific/Medical Publication:
Gastroenterology 2007;132:562-75
Reference:
Abstract/Summary:
Background & Aims: Increased inflammatory cytokine levels and intestinal epithelial cell apoptosis leading to disruption of epithelial integrity are major pathologic factors in inflammatory bowel diseases. The probiotic bacterium Lactobacillus rhamnosus GG (LGG) and factors recovered from LGG broth culture supernatant (LGG-s) prevent cytokine-induced apoptosis in human and mouse intestinal epithelial cells by regulating signaling pathways. Here, we purify and characterize 2 secreted LGG proteins that regulate intestinal epithelial cell antiapoptotic and proliferation responses. Methods: LGG proteins were purified from LGG-s, analyzed, and used to generate polyclonal antibodies for immunodepletion of respective proteins from LGG-conditioned cell culture media (CM). Mouse colon epithelial cells and cultured colon explants were treated with purified proteins in the absence or presence of tumor necrosis factor (TNF). Akt activation, proliferation, tissue injury, apoptosis, and caspase-3 activation were determined. Results: We purified 2 novel proteins, p75 (75 kilodaltons) and p40 (40 kilodaltons), from LGG-s. Each of these purified protein preparations activated Akt, inhibited cytokine-induced epithelial cell apoptosis, and promoted cell growth in human and mouse colon epithelial cells and cultured mouse colon explants. TNF-induced colon epithelial damage was significantly reduced by p75 and p40. Immunodepletion of p75 and p40 from LGG-CM reversed LGG-CM activation of Akt and its inhibitory effects on cytokine-induced apoptosis and loss of intestinal epithelial cells. Conclusions: p75 and p40 are the first probiotic bacterial proteins demonstrated to promote intestinal epithelial homeostasis through specific signaling pathways. These findings suggest that probiotic bacterial components may be useful for preventing cytokine-mediated gastrointestinal diseases.
Researcher(s):
Yan F et al.
Research Unit(s):
Departments of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Cell and Developmental Biology, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Title of research:
Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells.
Scientific/Medical Publication:
J Biol Chem 2002;277(5):50959-65
Reference:
http://www.jbc.org/content/277/52/50959.long
Abstract/Summary:
Probiotic bacteria are microorganisms that benefit the host by preventing or ameliorating disease. However, little information is known regarding the scientific rationale for using probiotics as alternative medicine. The purpose of this paper is to investigate the mechanisms of probiotic beneficial effects on intestinal cell homeostasis. We now report that one such probiotic,Lactobacillus rhamnosus GG (LGG), prevents cytokine-induced apoptosis in two different intestinal epithelial cell models. Culture of LGG with either mouse or human colon cells activates the anti-apoptotic Akt/protein kinase B. This model probiotic also inhibits activation of the pro-apoptotic p38/mitogen-activated protein kinase by tumor necrosis factor, interleukin-1α, or γ-interferon. Furthermore, products recovered from LGG culture broth supernatant show concentration-dependent activation of Akt and inhibition of cytokine-induced apoptosis. These observations suggest a novel mechanism of communication between probiotic microorganisms and epithelia that increases survival of intestinal cells normally found in an environment of pro-apoptotic cytokines.
Researcher(s):
Lu R et al.
Research Unit(s):
Mucosal Biology Research Center, Health Science Facility II, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Proteomic Core Facility, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Title of research:
Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2009;49(1):23-30
Reference:
Abstract/Summary:
Objectives: Diarrheal diseases remain a major human plague that still claim millions of lives every year. Probiotics, including Lactobacillus GG (LGG), are known to have a beneficial effect on diarrheal diseases, but their mechanism of action has not yet been completely established. Therefore, the main objective of this work was to identify and characterize moieties elaborated by LGG that exert antibacterial activity.
Materials and Methods: Lactobacillus GG conditional media was subjected to liquid chromatography/mass spectrometry. The identified peptides were synthesized by Symphony peptide synthesizer and purified by HPLC using Dynamax reverse-phase C18 column. Using A600 measurement and tested for their antibacterial activity.
Results: We identified 7 small peptides from LGG cultured media, 2 of which are NPSRQERR and PDENK, retained the antibacterial activity detected with LGG conditional media. The antibacterial activity was exerted against both Gram-negative (Escherichia coli EAEC 042 and Salmonella typhi) and, with less potency, Gram-positive (Staphylococcus aureus) bacteria.
Conclusions: Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity. NPSRQERR showed the most potent antibacterial effect that was detected both in Gram-negative and Gram-positive microorganisms. These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.
Researcher(s):
Forsyth CB et al.
Research Unit(s):
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, and Rush University Medical Center, Chicago, IL 60612, USA
Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA
Title of research:
Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.
Scientific/Medical Publication:
Alcohol 2009;43(2):163-172
Reference:
http://www.alcoholjournal.org/article/S0741-8329(09)00012-3/abstract
Abstract/Summary:
Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, “probiotic” Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague–Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5×107 live L. rhamnosus Gorbach–Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol+LGG (ALC+LGG)–fed rats had significantly (P≤.05) less severe ASH than ALC+V–fed rats. L. rhamnosus Gorbach–Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach–Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.
Researcher(s):
Forsyth CB et al.
Research Unit(s):
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, and Rush University Medical Center, Chicago, IL 60612, USA
Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA
Title of research:
Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.
Scientific/Medical Publication:
Alcohol 2009;43(2):163-172
Reference:
http://www.alcoholjournal.org/article/S0741-8329(09)00012-3/abstract
Abstract/Summary:
Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, “probiotic” Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague–Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5×107 live L. rhamnosus Gorbach–Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol+LGG (ALC+LGG)–fed rats had significantly (P≤.05) less severe ASH than ALC+V–fed rats. L. rhamnosus Gorbach–Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach–Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.
Researcher(s):
Wang Y et al.
Research Unit(s):
College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
Department of Medicine, University of Louisville, Louisville, Kentucky
Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky
Alcohol Research Center, University of Louisville, Louisville, Kentucky
School of Pharmacy, Wenzhou Medical College, Zhejiang, China
First Hospital, Xi'an Jiaotong University, Shaanxi, China
Robby Rex Veterans Affairs Medical Center, Louisville, Kentucky
Title of research:
Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury.
Scientific/Medical Publication:
Am J Physiol Gastrointest Liver Physiol 2012;303(1):G32-G41
Reference:
http://ajpgi.physiology.org/content/303/1/G32.long
Abstract/Summary:
Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (109 colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury.
Researcher(s):
Adawi D et al.
Research Unit(s):
Department of Surgery, Experimental Research, Malmö University Hospital, S-205 02, Malmö, Sweden
Department of Food Technology, Lund University, Lund, Sweden
Title of research:
Effects of different probiotic strains of Lactobacillus and Bifidobacterium on bacterial translocation and liver injury in an acute liver injury model.
Scientific/Medical Publication:
Int J Food Microbiol 2001;70:213-220
Reference:
http://www.sciencedirect.com/science/article/pii/S0168160501005505
Abstract/Summary:
Septic complications represent frequent causes of morbidity in liver diseases and following hepatic operations. Most infections are caused by the individual own intestinal microflora. The intestinal microflora composition is important in physiological and pathophysiological processes in the human gastrointestinal tract, but their influence on liver in different situations is unclear. We therefore studied the effect of different Lactobacillus strains and a Bifidobacterium strain on the extent of liver injury, bacterial translocation and intestinal microflora in an acute liver injury model.
Sprague–Dawley rats were divided into five groups: acute liver injury control, acute liver injury+B. animalis NM2, acute liver injury+L. acidophilus NM1, acute liver injury+L. rhamnosus ATCC 53103, and acute liver injury+L. rhamnosus DSM 6594 and L. plantarum DSM 9843. The bacteria were administered rectally daily for 8 days. Liver injury was induced on the 8th day by intraperitoneal injection of d-galactosamine (1.1 g/kg BW). Samples were collected 24 h after the liver injury. Liver enzymes and bilirubin serum levels, bacterial translocation (to arterial and portal blood, liver and mesenteric lymph nodes (MLNs)), and intestinal microflora were evaluated.
L. acidophilus NM1; L. rhamnosus ATCC 53103, and L. rhamnosus DSM 6594+L. plantarum DSM 9843 decreased bacterial translocation compared to the liver injury control group. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes. The levels of alanine aminotransferase (ALAT) were significantly lower in the L. acidophilus, L. rhamnosus ATCC 53103, L. rhamnosus DSM 6594+L. plantarum DSM 9843 groups compared to the liver injury group. The L. rhamnosus and L. rhamnosus+L. plantarum groups significantly reduced ALAT levels compared to the B. animalis group. All administered bacteria decreased the Enterobacteriaceae count in the cecum and colon.
Administration of different lactobacilli and a Bifidobacterium strain in an acute liver injury rat model, has shown different effects on bacterial translocation and hepatocellular damage. L. acidophilus, L. rhamnosus, and L. rhamnosus+L. plantarum reduced bacterial translocation and hepatocellular damage. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes and did not affect hepatocellular damage.
Researcher(s):
Bull-Otterson L et al.
Research Unit(s):
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
Department of Medicine, Alcohol Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA
Department of Bioinformatics and Biostatistics, University of Louisville School of Medicine, Louisville, Kentucky, USA
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA
Robley Rex VAMC, Louisville, Kentucky, USA
Title of research:
Metagenomic Analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillys rhamnosus GG treatment.
Scientific/Medical Publication:
PLOS One;8(1):e53028
Reference:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053028
Abstract/Summary:
Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD). Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v) for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG) from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3–V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.
Researcher(s):
Mutlu E et al.
Research Unit(s):
Rush University Medical Center, Division of Digestive Diseases and Nutrition Department of Internal Medicine, Division of Digestive Diseases, Nutrition Rush University Medical Center, Chicago, IL, USA
Microbiome Analysis Center, Department of Environmental Science and Policy, George Mason University, Fairfax, VA, USA
Title of research:
Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats.
Scientific/Medical Publication:
Alcohol Clin Exp Res. 2009;33:1836–1846
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684271/
Abstract/Summary:
Background:
Clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol-fed rats to see if chronic alcohol consumption affects gut bacteria composition.
Method:
Male Sprague-Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal-attached microbiota composition were interrogated by Length Heterogeneity PCR (LH-PCR) fingerprinting.
Results:
Bacterial microbiota composition in alcohol-fed rats is not different from dextrose fed rats at weeks 4 and 6. Mucosa-associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol-induced dysbiosis up to 10 weeks of alcohol treatment.
Conclusion:
Daily alcohol consumption for 10 weeks alters colonic mucosa- associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD.
Researcher(s):
Vendt N et al.
Research Unit(s):
--------------------------------------------------------------------------
Title of research:
Growth during the first 6 months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial.
Scientific/Medical Publication:
J Hum Nutr Dietet 2006;19:51-58
Reference:
2006;19:51-58
http://agris.fao.org/agris-search/search.do?recordID=US201301058182
Abstract/Summary:
Probiotic bacteria have beneficial effects on the immune system and gastrointestinal tract, but the impacts of their long-term consumption on health and growth in early infancy are not well documented. The aim of this study was to evaluate the influence of Lactobacillus rhamnosus GG (LGG)-enriched formula on growth and faecal microflora during the first 6 months of life in normal healthy infants. One hundred and twenty healthy infants (up to 2 months) received LGG-supplemented formula or regular formula in a double-blind, randomized manner until the age of 6 months. Weight, length and head circumference were measured monthly and transformed into standard deviation scores (SDS). Faecal samples were obtained from a random sample of infants (n = 25) at entry and at the end of the study. One hundred and five infants (51 in the LGG group) completed the study. Children receiving LGG-supplemented formula grew better: their changes in their length and weight SDS ([Delta]SDS) at the end of the study were significantly higher than those receiving regular formula (0.44 ± 0.37 versus 0.07 ± 0.06, P < 0.01 and 0.44 ± 0.19 versus 0.07 ± 0.06, P < 0.005, respectively). The LGG group had a significant, higher defecation frequency 9.1 ± 2.6 versus 8.0 ± 2.8 (P < 0.05). More frequent colonization with lactobacilli was found in the LGG group, 91% versus 76% (P < 0.05) at the end of the study. Infants fed with LGG-enriched formula grew better than those fed with regular formula.
Researcher(s):
Rouge C et al.
Research Unit(s):
INRA UMR 1280, Physiologie des Adaptations Nutritionnelles, INRA and University of Nantes, Human Nutrition Research Center, Nantes, France.
Neonatal Intensive Care Unit, Hopital Mere-et-Enfant, CHU de Nantes, France;
Nestec Research Center, Vers-Chez-les-Blancs, Switzerland
Ecosysteme Intestinal, Probiotiques, Antibiotiques, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Paris Descartes, Paris, France
Therapeutiques Cliniques et Experimentales des Maladies Infectieuses, University of Nantes, France
Neonatal Intensive Care Unit, Institut de Puericulture, Paris, France
Title of research:
Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial.
Scientific/Medical Publication:
Am J Clin Nutr 2009;89:1828-35
Reference:
http://agris.fao.org/agris-search/search.do?recordID=US201301633687
Abstract/Summary:
Background:
Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants, the mechanisms are unclear, and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants.
Objective:
The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight.
Design:
In a bicentric, double-blind, randomized controlled clinical trial that was stratified for center and birth weight, 45 infants received enteral probiotics (Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG; BB536-LGG) and 49 received placebo. The primary endpoint was the percentage of infants receiving >50% of their nutritional needs via enteral feeding on the 14th day of life. A triangular test was used to perform sequential analysis.
Results:
The trial was discontinued after the fourth sequential analysis concluded a lack of effect. The primary endpoint was not significantly different between the probiotic (57.8%) and placebo (57.1%) groups (P = 0.95). However, in infants who weighed >1000 g, probiotic supplementation was associated with a shortening in the time to reach full enteral feeding (P = 0.04). Other than colonization by the probiotic strains, no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed. No colonization by probiotic strains was detected in infants who weighed [less-than or equal to]1000 g, presumably because of more frequent suspensions of enteral feeding, more courses of antibiotic treatment, or both.
Conclusions:
Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing >1000 g. This trial was registered at clinicaltrials.gov as NCT 00290576.
Researcher(s):
LeBlanc JG et al.
Research Unit(s):
Centro de Referencia para Lactobacilos (CERELA-CONICET) Chacabuco 145, (T4000ILC) Tucumán, Argentina
Laboratory of Probiogenomics, Department of Genetics, Biology of Microorganisms, Anthropology and Evolution, University of Parma, Parma, Italy
Cátedra de Microbiología Superior, Universidad Nacional de Tucumán (UNT), (T4000INI) Tucumán, Argentina
Department of Microbiology & Alimentary Pharmabiotic Centre, Bioscience Institute, National University of Ireland Cork, Western Road, Cork, Ireland
Title of research:
Bacteria as vitamin suppliers to their host: a gut microbiota perspective.
Scientific/Medical Publication:
Curr Opin Biotechnol 2013;24(2):160-8
Reference:
http://www.sciencedirect.com/science/article/pii/S095816691200119X
Abstract/Summary:
Food-related lactic acid bacteria (LAB) as well as human gut commensals such as bifidobacteria can de novo synthesize and supply vitamins. This is important since humans lack the biosynthetic capacity for most vitamins and these must thus be provided exogenously. Although vitamins are present in a variety of foods, deficiencies still occur, mainly due to malnutrition as a result of insufficient food intake and because of poor eating habits. Fermented milks with high levels of B-group vitamins (such as folate and riboflavin) can be produced by LAB-promoted and possibly bifidobacteria-promoted biosynthesis. Moreover, certain strains of LAB produce the complex vitamin cobalamin (or vitamin B12). In this review, fermented foods with elevated levels of B-group vitamins produced by LAB used as starter cultures will be covered. In addition, genetic abilities for vitamin biosynthesis by selected human gut commensals will be discussed.
Researcher(s):
Wu GD et al.
Research Unit(s):
Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Instituto de Ciências Biológicas, Universidade Federal de Goiás Goiania, GO, Brazil.
Department of Computer Science, University of Colorado, Boulder, USA.
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, USA.
Department of Chemistry and Biochemistry, University of Colorado, Boulder, USA.
Howard Hughes Medical Institute, University of Colorado, Boulder, USA.
Division of Gastroenterology, Children’s Hospital of Philadelphia, Philadelphia, USA.
Title of research:
Linking long-term dietary patterns with gut microbial enterotypes.
Scientific/Medical Publication:
Science 2011;334:105-108
Reference:
http://www.sciencemag.org/content/334/6052/105.short
Abstract/Summary:
Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
Researcher(s):
Cox LM et al.
Research Unit(s):
Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA
Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA
Center for Health Informatics and Bioinformatics, NYU Langone Medical Center, New York, NY 10016, USA
Department of Radiology, NYU Langone Medical Center, New York, NY 10016, USA
Departments of Population Health (Biostatistics) and Environmental Medicine, NYU Langone Medical Center, New York, NY 10016, USA
Department of Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates
Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA 01536, USA
New York Harbor Department of Veterans Affairs Medical Center, New York, NY 10010, USA
New York Genome Center, New York, NY 10013, USA
Title of research:
Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences.
Scientific/Medical Publication:
Cell 2014:158(4):705-21
Reference:
http://www.cell.com/cell/abstract/S0092-8674(14)00821-6
Abstract/Summary:
Early life is a critical window of host-microbe metabolic interaction
Low-dose penicillin treatment amplifies diet-induced obesity
A transient early microbiota perturbation leads to long-term increased adiposity
The penicillin-altered microbiota has a causal role in inducing metabolic changes
Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations.
Researcher(s):
Cox AJ et al.
Research Unit(s):
Molecular Basis of Disease, Griffith University, Southport, Brisbane, QLD, Australia
Heart Foundation Research Centre, Griffith University, Southport, Brisbane, QLD, Australia
Griffith Health Institute, and School of Medical Science, Griffith University, Southport, Brisbane, QLD, Australia
Title of research:
Obesity, inflammation, and the gut microbiota.
Scientific/Medical Publication:
Lancet Diabetes Endocrinol 2014 doi:10.1016/S2213-8587(14)70134-2
Reference:
http://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70134-2/fulltext
Abstract/Summary:
As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.
Researcher(s):
Probert CS et al.
Research Unit(s):
Clinical Science at South Bristol, University of Bristol, UK
Centre for Research in Analytical, Materials and Sensor Sciences, University of the West of England, Bristol, United Kingdom
Title of research:
Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases.
Scientific/Medical Publication:
J Gastrointest Liver Dis 2009;18:337–343.
Reference:
http://www.jgld.ro/2009/3/12.html
Abstract/Summary:
The assessment of disease activity in various conditions may be performed using a range of different techniques. These include the use of non-invasive tests, such as acute phase inflammatory markers and simple radiological techniques, to more advanced invasive and complex modalities. Over the past two decades the analysis of volatile organic compounds (VOCs) in biological specimens has attracted a considerable amount of clinical interest. The investigation of VOCs, using a variety of analytical techniques, has shown a significant correlation between the pattern and concentration of VOCs and the occurrence of various diseases. This provides a potentially non-invasive means of diagnosis, monitoring of pathological processes and assessment of pharmacological response. It may be rapid, simple and acceptable to patients. In this paper we review the medical literature and research efforts that have been carried out over the past decades, and try to summarize the clinical implications of VOC analysis of various biological emanations including stool, breath and blood samples and their correlation with gastrointestinal and liver diseases.
Researcher(s):
Zhu L et al.
Research Unit(s):
Digestive Diseases and Nutrition Center, Department of Pediatrics, the State University of New York at Buffalo, Buffalo, NY
Department of Microbiology and Immunology, University of Rochester, Rochester, NY
Title of research:
Characterization of the gut microbiome in non-alcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH.
Scientific/Medical Publication:
Hepatology 2013;57:601– 609.
Reference:
Abstract/Summary:
Nonalcoholic steatohepatitis (NASH) is a serious liver disease associated with obesity. Characterized by metabolic syndrome, hepatic steatosis, and liver inflammation, NASH is believed to be under the influence of the gut microflora. Here, the composition of gut bacterial communities of NASH, obese, and healthy children was determined by 16S ribosomal RNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of patients and healthy controls. UniFrac-based principle coordinates analysis indicated that most of the microbiome samples clustered by disease status. Each group was associated with a unique pattern of enterotypes. Differences were abundant at phylum, family, and genus levels between healthy subjects and obese patients (with or without NASH), and relatively fewer differences were observed between obese and the NASH microbiomes. Among those taxa with greater than 1% representation in any of the disease groups, Proteobacteria, Enterobacteriaceae, and Escherichia were the only phylum, family and genus types exhibiting significant difference between obese and NASH microbiomes. Similar blood-ethanol concentrations were observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol levels. Conclusions: The increased abundance of alcohol-producing bacteria in NASH microbiomes, elevated blood-ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and, consequently, liver inflammation suggest a role for alcohol-producing microbiota in the pathogenesis of NASH. We postulate that the distinct composition of the gut microbiome among NASH, obese, and healthy controls could offer a target for intervention or a marker for disease.
Researcher(s):
Nosova T et al.
Research Unit(s):
Research Unit of Alcohol Diseases, University Central Hospital of Helsinki, Finland
Anaerobe Reference Laboratory, National Public Health Institute, Helsinki, Finland
Title of research:
Acetaldehyde production and metabolism by human indigenous and probiotic Lactobacillus and Bifidobacterium strains.
Scientific/Medical Publication:
Alcohol Alcohol 2000;35:561-568
Reference:
http://alcalc.oxfordjournals.org/content/35/6/561.long
Abstract/Summary:
Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to acetaldehyde. We examined whether human gastrointestinal lactobacilli (three strains), bifidobacteria (five strains) and probiotic Lactobacillus GG ATCC 53103 are also able to metabolize ethanol and acetaldehyde in vitro. Acetaldehyde production by bacterial suspensions was determined by gas chromatography after a 1-h incubation with 22 mM ethanol. To determine the acetaldehyde consumption, the suspensions were incubated with 50 μM or 500 μM acetaldehyde as well as with 500 μM acetaldehyde and 22 mM ethanol, i.e. under conditions resembling those in the human colon after alcohol intake. The influence of growth media and bacterial concentration on the ability of lactobacilli to metabolize acetaldehyde and to produce acetate from acetaldehyde were determined. ADH and aldehyde dehydrogenase (ALDH) activities were determined spectrophotometrically. Neither measurable ADH nor ALDH activities were found in aerobically grown Lactobacillus GG ATCC 53103 and Lactobacillus acidophilus ATCC 4356 strains. All the lactobacilli and bifidobacteria strains revealed a very limited capacity to oxidize ethanol to acetaldehyde in vitro. Lactobacillus GG ATCC 53103 had the highest acetaldehyde-metabolizing capacity, which increased significantly with increasing bacterial concentrations. This was associated with a marked production of acetate from acetaldehyde. The type of the growth media had no effect on acetaldehyde consumption. Addition of ethanol to the incubation media diminished the acetaldehyde-metabolizing capacity of all strains. However, in the presence of ethanol, Lactobacillus GG ATCC 53103 still demonstrated the highest capacity for acetaldehyde metabolism of all strains. These data suggest a beneficial impact of Lactobacillus GG ATCC 53103 on high gastrointestinal acetaldehyde levels following alcohol intake. The possible clinical implications of this finding remain to be established in in vitro studies.
Researcher(s):
Guarner F et al.
Research Unit(s):
Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain
Title of research:
Gut flora in health and disease.
Scientific/Medical Publication:
Lancet 2003;361:512-519
Reference:
http://www.sciencedirect.com/science/article/pii/S0140673603124890
Abstract/Summary:
The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.
Researcher(s):
Tilg H et al.
Research Unit(s):
Christian Doppler Research Laboratory for Gut Inflammation, and Department of Medicine II (Gastroenterology and Hepatology), Medical University Innsbruck, Innsbruck, Austria.
Title of research:
Obesity and the microbiota.
Scientific/Medical Publication:
Gastroenterol 2009;136:1476-148
Reference:
http://www.gastrojournal.org/article/S0016-5085(09)00440-5/abstract
Abstract/Summary:
------------
Researcher(s):
Backhed F et al.
Research Unit(s):
Center for Genome Sciences and Departments of Molecular Biology and Pharmacology, Genetics, and Medicine, Cell Biology, and Physiology, Washington University School of Medicine, St. Louis, MO 63110; Samuel Luenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
Biomedical Center, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea;
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada M5S 1A8
Title of research:
The gut microbiota as an environmental factor that regulates fat storage.
Scientific/Medical Publication:
Proc Natl Acad Sci USA 2004;101:15718-15723
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC524219/
Abstract/Summary:
New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.
Researcher(s):
Turnbaugh PJ et al.
Research Unit(s):
Center for Genome Sciences, Washington University, St. Louis, Missouri 63108, USA.
Genome Sequencing Center, Washington University, St. Louis, Missouri 63108, USA
Title of research:
An obesity-associated gut microbiome with increase capacity for energy harvest.
Scientific/Medical Publication:
Nature 2006;444;1027-1031102
Reference:
http://www.nature.com/nature/journal/v444/n7122/full/nature05414.html
Abstract/Summary:
The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
Researcher(s):
Turnbaugh PJ et al.
Research Unit(s):
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108, USA
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
Title of research:
The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice.
Scientific/Medical Publication:
Sci Transl Med 2009;1, 6ra14;doi:10.1126/scitranlmed.3000322
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894525/
Abstract/Summary:
Diet and nutritional status are among the most important, modifiable determinants of human health. The nutritional value of food is influenced in part by a person’s gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelationships between diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent, metagenomic analysis of the temporal, spatial and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized, and reproduced much of the bacterial diversity of the donor’s microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat/high-sugar “Western” diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community, but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle “clinical trials” that test the effects of environmental and genetic factors on the gut microbiota and host physiology.
Researcher(s):
Cummings JH et al.
Research Unit(s):
Medical Research Council Dunn Clinical Nutrition Centre, Cambridge, UK.
Title of research:
Role of intestinal bacteria in nutrient metabolism.
Scientific/Medical Publication:
J Parenter Enter Nutr 1997;21:357-365
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894525/pdf/nihms209492.pdf
Abstract/Summary:
The human large intestine contains a microbiota, the components of which are generically complex and metabolically diverse. Its primary function is to salvage energy from carbohydrate not digested in the upper gut. This is achieved through fermentation and absorption of the major products, short chain fatty acids (SCFA), which represent 40-50% of the available energy of the carbohydrate. The principal SCFA, acetate, propionate and butyrate, are metabolized by the colonic epithelium (butyrate), liver (propionate) and muscle (acetate). Intestinal bacteria also have a role in the synthesis of vitamins B and K and the metabolism of bile acids, other sterols and xenobiotics. The colonic microflora are also responsive to diet. In the presence of fermentable carbohydrate substrates such as non-starch polysaccharides, resistant starch and oligosaccharides, bacteria grow and actively synthesize protein. The amount of protein synthesis and turnover within the large intestine is difficult to determine, but around 15 g biomass is excreted in faeces each day containing 1 g bacterial-N. Whether bacterially synthesized amino acids are ever absorbed from the colon remains unclear. Finally, individual colonic micro-organisms such as sulphate-reducing bacteria, bifidobacteria and clostridia, respond selectively to specific dietary components in a way that may be important to health.
Researcher(s):
Sutas Y et al.
Research Unit(s):
University of Tampere, Medical School, Tampere
Agricultural Research Centre of Finland, Food Research Institute, Jokioinen
Valio Ltd, Research & Development Centre, Helsinki
University of Helsinki, Department of Food Technology, Dairy Sciences, Helsinki.
Title of research:
Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolysed with Lactobacillus casei GG-derived enzymes.
Scientific/Medical Publication:
J Allergy Clin Immunol 1996;98:216-224
Reference:
http://www.jacionline.org/article/S0091-6749(96)70245-2/abstract
Abstract/Summary:
Background:
Processing of proteins in the gut and activation of T-cell suppression leads to systemic hyporesponsiveness to ingested protein antigens.
Objective:
The study was designed to determine whether lactobacilli, a major part of human intestinal microflora, can contribute to degradation of food antigens in the gut and modify their immunoactivities.
Methods:
Lymphocyte transformation tests were carried out in healthy adults to determine the mitogen-induced lymphocyte proliferative responses to bovine caseins hydrolyzed with pepsin and trypsin and to bovine caseins additionally hydrolyzed with enzymes derived from Lactobacillus casei strain GG (ATCC 53103).
Results:
In experiments done with caseins hydrolyzed with pepsin and trypsin, β- and α s1-caseins significantly suppressed the proliferation of lymphocytes at 0.1 and 10 μg/ml, respectively, when compared with corresponding control cultures without these hydrolysates. In contrast, κ-casein significantly stimulated the proliferation of lymphocytes at 10 μg/ml. In experiments done with caseins additionally hydrolyzed with L. casei GG–derived enzymes, there was one consistent effect on lymphocyte proliferation: suppression by α s1-, β-, and κ-caseins at 0.1, 10, and 1000 μg/ml, respectively.
Conclusions:
Hydrolysis of caseins with L. casei GG–derived enzymes generates molecules with suppressive effects on lymphocyte proliferation. In addition, intestinal bacteria can be beneficial in the downregulation of hypersensitivity reactions to ingested proteins in patients with food allergy.
Researcher(s):
Sutas Y et al.
Research Unit(s):
Tampere University Medical School, Tampere University Hospital, Department of Pediatrics, Tampere
Tampere University Medical School and Tampere University Hospital, Department of Microbiology and Immunology, Tampere, Finland
Title of research:
Down-Regulation of Anti-CD3 Antibody-Induced IL-4 Production by Bovine Caseins Hydrolysed with Lactobacillus GG–Derived Enzymes.
Scientific/Medical Publication:
Scand J Immunol 1996;43:687-689
Reference:
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-3083.1996.d01-258.x/abstract
Abstract/Summary:
A prerequisite for systemic hyporesponsiveness to dietary antigens is their processing in the gut. This study investigated whether bovine caseins degraded by enzymes of an intestinal bacterial strain, Lactobacillus GG (ATCC 53103), could regulate the cytokine production by anti-CD3 antibody-induced peripheral blood mononuclear cells of 14 atopic patients, aged 5–29 (mean, 16) months. Purified casein up-regulated the interleukin-4 and interferon-γ production, P = 0.008 and P = 0.008, respectively. Conversely, Lactobacillus GG-degraded casein down-regulated the interleukin-4 production, P = 0.003, with no effect on interferon-γ. These results indicate that intestinal bacteria may modify immunomodulatory properties of native food proteins and introduce a promising tool to provide protection from potentially harmful dietary antigens at a young age.
Researcher(s):
Pessi T et al.
Research Unit(s):
Department of Paediatrics, University of Turku, FIN-20521 Turku, Finland
Department of Respiratory Medicine, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland
Department of Clinical Chemistry and Clinical Microbiology, Tampere University Hospital, Medical School, University of Tampere, Tampere, Finland
Title of research:
Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.
Scientific/Medical Publication:
Int Immunopharmacol 2001;1(12):211-8
Reference:
http://www.sciencedirect.com/science/article/pii/S1567576900000187
Abstract/Summary:
Earlier data indicate that Lactobacillus rhamnosus GG ATCC 53103 (L. GG), a commensal intestinal bacterial strain, promotes the degradation of proteins in the gut in vivo, and bovine casein hydrolysed with L. GG-derived proteases suppresses lymphocyte proliferation in vitro. The present study aimed to evaluate the effect of L. GG-degraded bovine casein on T-cell activation, i.e. IL-2 mRNA expression and protein kinase C (PKC) translocation. To this end, Northern blot analyses for IL-2 mRNA expression and PKC assays with and without L. GG-degraded casein were carried out on T cells isolated from 11 healthy adults. Cell cultures in 8–11 experiments contained 1 mg ml−1 bovine casein in degraded or undegraded form in the presence of a mitogen, i.e. phorbol 12,13-dibutyrate plus calcium ionophore (PBDu+A23187) or anti-CD3. Also IL-2, IL-4 and IFN-γ syntheses were determined in 24-h culture supernatants. IL-2 mRNA expression was reduced in experiments with L. GG-degraded casein. In parallel, the IL-2 concentration in PBDu+A23187-stimulated culture supernatants, expressed as geometric means (95% confidence interval), decreased from 15,892 (7174–35,203) pg ml−1 to 4744 (2095–10,742) pg ml−1 when containing L. GG-degraded casein. L. GG-degraded casein inhibited PKC translocation, the action resembling that of PKC inhibitor, RO31-8220. These results extend previous data on L. GG-degraded casein, showing in vitro the suppression of T-cell activation.
Researcher(s):
Siigur U et al.
Research Unit(s):
Laboratory Department, Tartu University Hospital, Tartu, Estonia
Laboratory of Medical Microbial Ecology, Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
Children's Hospital of Tartu University, Tartu, Estonia
Department of Biochemistry and Food Chemistry, University of Turku, Finland
Read More:
http://informahealthcare.com/doi/abs/10.3109/08910609609166467
Title of research:
Effect of bacterial infection and administration of a probiotic on faecal short-chain fatty acids.
Scientific/Medical Publication:
Microb Ecol Health Dis 1996;9:271-277
Reference:
http://www.microbecolhealthdis.net/index.php/mehd/article/viewArticle/8389
Abstract/Summary:
Faecal short-chain fatty acids (SCFAs) were determined in children with shigellosis (n=22) or salmonellosis (n=11) prior to treatment and 5 d and 10 d after treatment with an antibacterial drug (TMP-SMX or Polymyxin, 5 d), or Lactobacillus GG (1010 - 1011 CFU/d, 10 d), or both had been started. At admission the SCFA concentrations were very low. Acetic, propionic and iso-valeric acid were significantly higher in shigellosis than in salmonellosis. The SCFA concentrations increased significantly during treatment, reaching those of adults by the 5th day and exceeding them by the 10th day, and showed no difference between the diseases after the 1st day. Adminsitration of Lactobacillus GG resulted in increased concentration of propionic acid by the 5th day of treatment and difference in iso-caproic acid in the 10th day samples: it was not found in any child who had received Lactobacillus GG but was present in half of the samples from the group treated solely with antibacterial drug. Iso-caproic acid is not found in healthy adults and may be indicative of Clostridium difficile. The disturbances in microbial ecology of the gut in enteric infections may have different characteristics depending on the aetiological agent. Treatment with Lactobacillus GG promotes recovery of the ecosystem as reflected by the faecal SCFAs.
Researcher(s):
Hosoda M et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Japan
Japan Collection of Microorganisms, The Institute of Physical and Chemical Research (RIKEN),
Title of research:
Effects of Lactobacillus GG strain intake on fecal microflora and defecation in healthy volunteers.
Scientific/Medical Publication:
Bifidus 1994:8:21-28
Reference:
https://www.jstage.jst.go.jp/article/jim1987/8/1/8_1_21/_article/-char/ja/
Abstract/Summary:
Effects of LactobacillusGG yoghurt administration on the composition of fecal bacteria and properties were tested in eight healthy Japanese volunteers. The volumes of intake of the yoghurt were 90g/day for 10 days and then 300g/day for 10 days continuously. During the intake of the yoghurt, the numbers of bifidobacteria and lactobacilli in the feces of all volunteers were significantly increased, whereas the number of lecithinase-negative clostridia was significantly decreased. The fecal ammonia concentration during the yoghurt feeding was lower than those before and after the intake.
Researcher(s):
Cummings JH et al.
Research Unit(s):
MRC Dunn Clinical Nutrition Centre, Cambridge.
Department of Histopathology, Addenbrooke’s Hospital, Cambridge
Title of research:
Short chain fatty acids in human large intestine, portal, hepatic and venous blood.
Scientific/Medical Publication:
Gut 1987;28(10):1221-7
Reference:
http://gut.bmj.com/content/28/10/1221.long
Abstract/Summary:
Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
Researcher(s):
Wong JM et al.
Research Unit(s):
Clinical Nutrition and Risk Factor Modification Center, St Michael's Hospital, Canada
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto. Ont, Canada
Department of Medicine, Division of Endocrinology and Metabolism, St Michael's Hospital, Canada
Department of Medicine, Faculty of Medicine, University of Toronto, Toronto. Ont, Canada
Title of research:
Colonic health: fermentation and short chain fatty acids.
Scientific/Medical Publication:
J Clin Gastroenterol 2006;40(3):235-243
Reference:
Abstract/Summary:
Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.
Researcher(s):
Cox MJ et al.
Research Unit(s):
Division of Gastroenterology, University of California San Francisco, San Francisco, California, USA
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
Ecology Department, Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
Title of research:
Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome.
Scientific/Medical Publication:
PLoS One 2010;5(1):e8745
Reference:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008745
Abstract/Summary:
Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community.
Researcher(s):
Benno et al.
Research Unit(s):
Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Japan
Japan Collection of Microorganisms, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan
Department of Practical Arts and Science, Showa Women’s University, Tokyo, Japan
Title of research:
Effects of Lactobacillus GG yogurt on human intestinal microecology in Japanese subjects.
Scientific/Medical Publication:
Nutrition Today 1996;(31)6:9s-11S
Reference:
Abstract/Summary:
Consumption of Lactobacillus GG yogurt by normal healthy Japanese subjects resulted in increased the numbers of fecal bifidobacteria and Lactobacillus GG, and decreased fecal ammonia concentration as well as decreased fecal pH. Beneficial effects were observed during the yogurt intake, and values returned to normal after completing treatment.
Researcher(s):
Sepp E et al.
Research Unit(s):
Department of Clinical Microbiology, Institute of General and Molecular Pathology of Tartu University and Tartu University Hospital, Helsinki, Finland
Institute of Microbiology, University of Tartu, Tartu, Estonia
Department of Food Chemistry, University of Helsinki, Helsinki, Finland
Read More:
http://informahealthcare.com/doi/abs/10.3109/08910609309141340
Title of research:
Effect of administration of Lactobacillus casei strain GG on the gastrointestinal microbiota of newborns.
Scientific/Medical Publication:
Microb Ecol Health Dis 1993;6:309-314
Reference:
http://informahealthcare.com/doi/abs/10.3109/08910609309141340
Abstract/Summary:
The aim of the study was to determine whether Lactobacillus casei strain GG could colonise the intestine of newborns and the influence of its administration on establishment of the microbiota. The faecal bacterial population of 25 under 1 mth old newborns was studied: in addition to breastfeeding, 15 babies (GG group) received for 2 wk immediately after birth Lactobacillus GG supplement as freeze-dried powder diluted in water in a dose of 1010-1011 c.f.u./g; 10 newborns (control group) did not receive any supplement to breastfeeding. The faecal bacterial composition of meconium was similar in both groups studied. Ten newborns (67 per cent) excreted Lactobacillus GG, while in eight cases (53-3 per cent) Lactobacillus GG was found even 2 wk after the administration was stopped. The faecal concentrations and the relative proportion of Lactobacillus GG were individually different. In 3-4 d, 5-7 d and 1 mth old newborns of the GG group the faecal concentrations of lactobacilli exceeded those of the control group. The faecal microorganisms predominance pattern did not differ in the case of 1 wk and 1 mth old newborns of the GG group. The study shows that 2 wk administration of Lactobacillus GG, which starts right after birth, increases intestinal lactobacilli concentrations and does not impair the establishment of a normal faecal bacterial microbiota.
Researcher(s):
Agarwal R et al.
Research Unit(s):
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Title of research:
Effect of oral Lactobacillus GG on enteric microflora in low-birth-weight neonates.
Scientific/Medical Publication:
J Pediatr Gastroenterol Nutr 2003;36:397-402
Reference:
http://journals.lww.com/jpgn/Abstract/2003/03000/Effects_of_Oral_Lactobacillus_GG_on_Enteric.19.aspx
Abstract/Summary:
Background:
Colonization patterns, especially by anaerobic flora, may play an important role in neonatal gut function. Probiotics could affect disease risk either directly through colonization or indirectly by promoting changes in gut microbial ecology.
Methods: To study the ability of Lactobacillus GG (LGG) to colonize the neonatal gut and modify its microbial ecology, a prospective, randomized study was performed in 71 preterm infants of less than 2000 g birth weight. Infants less than 1500 g (24 treated, 15 control) received 109 LGG orally twice daily for 21 days. Those infants weighing 1500 to 1999 g (23 treated, 9 control) were treated for 8 days. Stools were collected before treatment and on day 7 to 8 (and day 14 and 21, in the infants weighing less than 1500 g) for quantitative aerobic and anaerobic cultures.
Results:
Colonization with LGG occurred in 5 of 24 (21%) infants who weighed less than 1500 g versus 11 of 23 (47%) in larger infants. Colonization was limited to infants who were not on antibiotics within 7 days of treatment with LGG. There was a paucity of bacterial species at baseline, although larger infants had more bacterial species (1.59 ± 0.13 (SEM) vs 1.11 ± 0.12;P < 0.03) and higher mean log colony forming units (CFU) (8.79 ± 0.43 vs 7.22 ± 0.63;P < 0.05) compared with infants weighing less than 1500 g LGG. Treatment in infants weighing less than 1500 g resulted in a significant increase in species number by day 7, with further increases by day 21. This increase was mainly the result of increased Gram (+) and anaerobic species. No difference in species number was noted in controls. Mean log CFU of Gram (−) bacteria did not change in treated infants weighing less than 1500 g. However, Gram (+) mean log CFU showed a significant increase on day 21 (6.1 ± 0.9) compared with day 0 (3.5 ± 0.9) (P < 0.05). No significant changes in species number or quantitative counts were noted after LGG treatment in the infants weighing 1500 to 1999 g LGG was well tolerated in all infants.
Conclusion:
The neonatal response to a probiotic preparation is dependent on gestational and post-natal age and prior antibiotic exposure. Although LGG is a relatively poor colonizer in infants, especially those infants weighing less than 1500 g at birth, it does appear to affect neonatal intestinal colonization patterns.
Researcher(s):
Rokka T et al.
Research Unit(s):
Technical Research Centre of Finland, Chemical Technology, Helsinki, Finland
Title of research:
Release of bioactive peptides by enzymatic proteolysis of Lactobacillus GG fermented UHT milk.
Scientific/Medical Publication:
Milchwissenschaft 1997;52(12):675-677 (Milk Science International)
Reference:
http://cat.inist.fr/?aModele=afficheN&cpsidt=10572001
Abstract/Summary:
-------
Researcher(s):
Guarino MP et al.
Research Unit(s):
Department of Digestive Diseases, Campus Biomedico University, Via Alvaro del Portillo, Rome, Italy.
Title of research:
Effect of acute mucosal exposure to Lactobacillus rhamnosus GG on human colonic smooth muscle cells.
Scientific/Medical Publication:
J Clin Gastroentorol 2008;42(Suppl 3) Pt 2:S185-190
Reference:
Abstract/Summary:
Aim:
To define whether human colonic mucosa exposure to Lactobacillus rhamnosus GG (LGG), American Type Culture Collection (ATCC) 53103, may influence intestinal muscle cell contractility.
Methods:
Human colon specimens were obtained from disease-free margins of resected segments for cancer. The mucosa and submucosa, after dissection, were sealed between 2 chambers, with the luminal side of the mucosa facing upward and covered with 5 mL of Krebs solution and the submucosal side facing downward into 20 mL of Krebs solution. LGG or normal undernatant (N-undernatant) were added to the luminal side of the mucosa for 30 minutes. Smooth muscle cells (SMCs), isolated from the circular muscle layer, were exposed to undernatant for 30 minutes from the submucosal chamber of mucosa that was either preexposed to N-undernatant or to LGG (36×10−9 colony forming units/mL) (LGG-undernatant). Acetylcholine (Ach) dose-response was obtained for SMCs.
Results:
SMCs exposed to N-undernatant presented a dose-response to Ach (maximal contraction: 32%±5% with 1-μM Ach) that is similar to unstimulated SMCs. Exposure to LGG-undernatant resulted both in an 18%±3% cell shortening and a 78%±7% inhibition of maximal Ach-induced contraction. When SMCs were directly exposed to LGG, a significant impairment of contraction (70%±5%, compared with control cells) and a dose-dependent and time-dependent shortening were observed.
Conclusions:
After acute exposure of colonic mucosa to LGG, a significant shortening of SMCs is observed that possibly contributes to the reduced contractile response to Ach. Further studies are needed to establish the mechanisms of this effect that could account for the clinical efficacy of probiotics in intestinal disorders.
Researcher(s):
Hongisto SM et al.
Research Unit(s):
Valio Ltd, R&D, Helsinki, Finland
Foundation for Nutrition Research, Helsinki, Finland
Department of Allergy, Helsinki University Central Hospital, Helsinki, Finland
Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
Title of research:
A combination of fibre-rich rye bread and yoghurt containing Lactobacillus GG improves bowel function in women with self-reported constipation.
Scientific/Medical Publication:
Eur J Clin Nutr. 2006;60:319-324
Reference:
http://www.nature.com/ejcn/journal/v60/n3/full/1602317a.html
Abstract/Summary:
Objective:
The aim of the study was to investigate the effects of fibre-rich rye bread and yoghurt containing Lactobacillus GG (LGG) on intestinal transit time and bowel function, and to test whether they have an interaction in cases of self-reported constipation.
Design:
The study was carried out as a two-by-two factorial design.
Setting:
Free-living subjects.
Subjects:
A total of 59 healthy women with self-reported constipation, recruited by advertisement.
Interventions:
After a baseline period, the subjects were randomized into four diet groups: (1) rye bread+LGG yoghurt, (2) rye bread, (3) LGG yoghurt, and (4) control. The 3-week dietary intervention was followed by a 3-week follow-up period. During each period, total intestinal transit time was measured and the subjects recorded faecal frequency and consistency, difficulty in defecation and gastrointestinal symptoms.
Results:
The rye bread shortened total intestinal transit time (mean difference, -0.7; CI95, -1.1 to -0.2; P=0.007), increased faecal frequency (0.3; CI95, 0.1 to 0.5; P=0.001), softened faeces (-0.3; CI95, -0.4 to -0.2; P<0.001) and made defecation easier (-0.4; CI95, -0.5 to -0.2; P<0.001), but also increased gastrointestinal symptoms (1.6; CI95, 0.7 to 2.4; P<0.001) compared to the low-fibre toast consumed in the LGG and control groups. There were fewer symptoms in the rye bread+LGG group compared to the rye bread group (-1.3; CI95, -2.4 to -0.2; P=0.027).
Conclusions:
Fibre-rich rye bread can be recommended in the treatment of constipation, and the simultaneous consumption of LGG yoghurt relieves the adverse gastrointestinal effects associated with increased intake of fibre.
Researcher(s):
Laitinen K et al. and the Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota Group
Research Unit(s):
Department of Biochemistry and Food Chemistry, University of Turku, 20014 Turku, Finland
Functional Foods Forum, University of Turku, 20014 Turku, Finland
Stat-Consulting, 33230 Tampere, Finland
Department of Paediatrics, University of Turku, 20014 Turku, Finland
Department of Paediatrics, Turku University Central Hospital, 20520 Turku, Finland
Title of research:
Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial.
Scientific/Medical Publication:
Br J Nutr 2009;101:1679-1687
Reference:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=5830464
Abstract/Summary:
Balanced glucose metabolism ensures optimal fetal growth with long-term health implications conferred on both mother and child. We examined whether supplementation of probiotics with dietary counselling affects glucose metabolism in normoglycaemic pregnant women. At the first trimester of pregnancy 256 women were randomised to receive nutrition counselling to modify dietary intake according to current recommendations or as controls; the dietary intervention group was further randomised to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12; diet/probiotics) or placebo (diet/placebo) in a double-blind manner, whilst the control group received placebo (control/placebo). Blood glucose concentrations were lowest in the diet/probiotics group during pregnancy (baseline-adjusted means 4·45, 4·60 and 4·56 mmol/l in diet/probiotics, diet/placebo and control/placebo, respectively; P = 0·025) and over the 12 months' postpartum period (baseline-adjusted means 4·87, 5·01 and 5·02 mmol/l; P = 0·025). Better glucose tolerance in the diet/probiotics group was confirmed by a reduced risk of elevated glucose concentration compared with the control/placebo group (OR 0·31 (95 % CI 0·12, 0·78); P = 0·013) as well as by the lowest insulin concentration (adjusted means 7·55, 9·32 and 9·27 mU/l; P = 0·032) and homeostasis model assessment (adjusted means 1·49, 1·90 and 1·88; P = 0·028) and the highest quantitative insulin sensitivity check index (adjusted means 0·37, 0·35 and 0·35; P = 0·028) during the last trimester of pregnancy. The effects observed extended over the 12-month postpartum period. The present study demonstrated that improved blood glucose control can be achieved by dietary counselling with probiotics even in a normoglycaemic population and thus may provide potential novel means for the prophylactic and therapeutic management of glucose disorders.
Researcher(s):
Tabuchi M et al.
Research Unit(s):
Yonezawa Women's College of Yamagata PrefectureYonezawa 992-0025, Japan
Technical Research Laboratory, Takanashi Milk Products Co., Ltd.Yokohama 241-0023, Japan
Graduate School of Agriculture, Shinshu UniversityNagano-Minamiminowa 399-4598, Japan
Title of research:
Antidiabetic effect of Lactobacillus GG in Streptozotocin-induced diabetic rats.
Scientific/Medical Publication:
Biosci Biotechnol Biochem 2003;67(6):1421-1424
Reference:
http://www.tandfonline.com/doi/abs/10.1271/bbb.67.1421#.U--XHVaRBIc
Abstract/Summary:
Neonatally streptozotocin-induced diabetic (n-STZ) rats were given food containing Lactobacillus GG cells (GG) or a control diet (control), from 9 to 18 weeks of age. The GG cells significantly lowered the blood hemoglobin A1C (HbA1C) level and improved glucose tolerance in n-STZ rats (p<0.05). In the GG group, the serum insulin level at 30 min after glucose loading was significantly higher than in the control group (p<0.05).
Researcher(s):
Al-Hosni M et al.
Research Unit(s):
Department of Pediatrics, Saint Louis University School of Medicine, St Louis, MO, USA
Department of Pediatrics, St John Hospital & Medical Center, Detroit, MI, USA
Neonatal Intensive Care Unit, Cardinal Glennon Children's Medical Center, St Louis, MO, USA
Department of Pediatrics, UC Davis Children's Hospital, Sacramento, CA, USA
Department of Pediatrics, Vermont Children's Hospital at Fletcher Allen Health Care, Burlington, VT, USA
General Clinical Research Center, University of Vermont College of Medicine, Burlington, VT, USA
Clinical Trial Unit, Vermont Oxford Network, Burlington, VT, USA
Department of Pediatrics, University of Vermont College of Medicine, Burlington, VT, USA
Title of research:
Probiotics-supplemented feeding in extremely low-birth-weight infants.
Scientific/Medical Publication:
J Perinatol 2012;32(4):253-9
Reference:
http://www.nature.com/jp/journal/v32/n4/abs/jp201151a.html
Abstract/Summary:
Objective:
The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight (ELBW) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age (PMA). Other important outcome measures, such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated.
Study Design:
We conducted a multicenter randomized controlled double-blinded clinical study. The probiotics-supplementation (PS) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks (PMA). The control (C) group received unsupplemented feedings. Infant weight and feeding volumes were recorded daily during the first 28 days of study period. Weights were also recorded at 34 weeks PMA.
Result:
A total of 101 infants were enrolled (PS 50 versus C 51). There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA (PS group 58% versus C group 60%, (P value 0.83)) or in the average volume of feeding during 28 days after study entry (PS group 59 ml kg−1 versus C group 71 ml kg−1, (P value 0.11)). Calculated growth velocity was higher in the PS group compared with the C group (14.9 versus 12.6 g per day, (P value 0.05)). Incidences of necrotizing enterocolitis (NEC), as well as mortality were similar between the two groups.
Conclusion:
Although probiotic-supplemented feedings improve growth velocity in ELBW infants, there was no improvement in the percentage of infants with growth delay at 34 weeks PMA. There were no probiotic-related adverse events reported.
Researcher(s):
Bruzzese E et al.
Research Unit(s):
Department of Pediatrics, University of Naples ‘‘Federico II’’, Via S. Pansini 5, 80131 Naples, Italy
Institute of Child Health, University College London, London, UK
European Institute of Research in Cystic Fibrosis, Verona, Italy
Title of research:
Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study.
Scientific/Medical Publication:
Clin Nutr 2007;26(3):322-8
Reference:
http://www.clinicalnutritionjournal.com/article/S0261-5614(07)00029-5/abstract
Abstract/Summary:
Background & aims:
Probiotics reduce intestinal inflammation in children with cystic fibrosis (CF). We want to determine the effects of Lactobacillus GG (LGG) on pulmonary exacerbations in CF.
Methods:
A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV1), and modifications of body weight.
Results:
Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5–1.5; p=0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI95% 1.0–1.5; p=0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV1 (3.6%±5.2 vs. 0.9%±5; p=0.02) and body weight (1.5kg±1.8 vs. 0.7kg±1.8; p=0.02).
Conclusions:
LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.
Researcher(s):
Ilmonen J et al.
Research Unit(s):
Department of Clinical Sciences, University of Turku, 20014 Turku, Finland
Department of Paediatrics, Turku University Hospital, 20520 Turku, Finland
Stat-Consulting, 37130 Nokia, Finland
Functional Foods Forum, University of Turku, 20014 Turku, Finland
Department of Biochemistry and Food Chemistry, University of Turku, 20014 Turku, Finland
Title of research:
Impact of dietary counselling and probiotic intervention on maternal anthropometric measurements during and after pregnancy: A randomized placebo-controlled trial.
Scientific/Medical Publication:
Clin Nutr 2011;30(2):156-164
Reference:
http://www.clinicalnutritionjournal.com/article/S0261-5614(10)00182-2/abstract
Abstract/Summary:
Background & aims:
To establish whether probiotic supplemented dietary counselling influences maternal anthropometric measurements during and after pregnancy.
Methods:
At the first trimester of pregnancy 256 women were randomly assigned to receive nutrition counselling to modify dietary intake according to current recommendations or as controls; dietary intervention groups were further randomized to receive probiotics Lactobacillus rhamnosus GG (ATCC 53103) and Bifidobacterium lactis (diet/probiotics) or placebo (diet/placebo) capsules in a double-blind manner, whilst the controls received placebo (control/placebo). The intervention lasted until the end of exclusive breastfeeding for up to six months.
Results:
The risk of central adiposity defined as waist circumference 80 cm or more was lowered in women in the diet/probiotics group compared with the control/placebo group (OR 0.30, 95%CI 0.11–0.85, p = 0.023 adjusted for baseline BMI), whilst the diet/placebo group did not differ from the controls (OR 1.00, 95% CI 0.38–2.68, p = 0.994) at 6 months postpartum. The number needed to treat (NNT) with diet/probiotics to prevent one woman from developing a waist circumference of 80 cm or more was 4. Healthy eating pattern at 12 months postpartum (p = 0.001) and BMI prior to pregnancy (p < 0.001) were strong determinants of BMI at 12 months postpartum when adjusted for dietary intervention and exercise.
Conclusion:
The impact of probiotics-supplemented dietary counselling on central adiposity, may offer a novel means for the prevention and management of obesity.
Researcher(s):
Luoto R et al.
Research Unit(s):
Department of Pediatrics, Turku University Hospital, Turku, Finland
Department of Clinical Sciences, University ofTurku, Turku, Finland
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Functional Foods Forum, University of Turku, Turku, Finland
Title of research:
The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years.
Scientific/Medical Publication:
Int J Obes (2010) 34, 1531–1537
Reference:
http://agris.fao.org/agris-search/search.do?recordID=US201301929656
Abstract/Summary:
Background:
The achievements in combating the increasing trend of overweight and obesity have thus far been inadequate. The recently discovered instrumental role of the gut microbiota in host metabolism may offer a novel target in the prevention and management of obesity.
Objective:
To evaluate the impact of perinatal probiotic intervention on childhood growth patterns and the development of overweight during a 10-year follow-up.
Patients and methods:
Altogether 159 women were randomized and double-blinded to receive probiotics (1 × 1010 colony-forming units of Lactobacillus rhamnosus GG, ATCC 53103) or placebo 4 weeks before expected delivery; the intervention extending for 6 months postnatally. Anthropometric measurements of the children were taken at the ages of 3, 6, 12 and 24 months and at 4, 7 and 10 years in 113 (72%) children.
Results:
The excessive weight gain was detected to be two-parted; the initial phase of excessive weight gain initiating during fetal period and continuing until 24–48 months of age and a second phase of excessive weight gain starting after the age of 24–48 months. The perinatal probiotic intervention appeared to moderate the initial phase of excessive weight gain, especially among children who later became overweight, but not the second phase of excessive weight gain, the impact being most pronounced at the age of 4 years (P=0.063, analysis of variance for repeated measures). The effect of intervention was also shown as a tendency to reduce the birth-weight-adjusted mean body mass index at the age of 4 years (P=0.080, analysis of covariance).
Conclusions:
Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life. This novel observation calls for further epidemiological and clinical trials, with precise data on early growth patterns and on confounding factors influencing weight development.
Researcher(s):
Ritze Y et al.
Research Unit(s):
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
Department of Nutritional Science, Friedrich-Schiller-University, Jena, Germany
MVZ Institute of Microecology, Herborn, Germany
Title of research:
Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice.
Scientific/Medical Publication:
PLoS ONE (2014) 9(1):e80169.doi:10.1371/journal.pone.0080169
Reference:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0080169
Abstract/Summary:
Objective:
Experimental evidence revealed that obesity-associated non-alcoholic fatty liver disease (NAFLD) is linked to changes in intestinal permeability and translocation of bacterial products to the liver. Hitherto, no reliable therapy is available except for weight reduction. Within this study, we examined the possible effect of the probiotic bacterial strain Lactobacillus rhamnosus GG (LGG) as protective agent against experimental NAFLD in a mouse model.
Methods:
Experimental NAFLD was induced by a high-fructose diet over eight weeks in C57BL/J6 mice. Fructose was administered via the drinking water containing 30% fructose with or without LGG at a concentration resulting in approximately 5×107 colony forming units/g body weight. Mice were examined for changes in small intestinal microbiota, gut barrier function, lipopolysaccharide (LPS) concentrations in the portal vein, liver inflammation and fat accumulation in the liver.
Results:
LGG increased beneficial bacteria in the distal small intestine. Moreover, LGG reduced duodenal IκB protein levels and restored the duodenal tight junction protein concentration. Portal LPS (P≤0.05) was reduced and tended to attenuate TNF-α, IL-8R and IL-1β mRNA expression in the liver feeding a high-fructose diet supplemented with LGG. Furthermore liver fat accumulation and portal alanine-aminotransferase concentrations (P≤0.05) were attenuated in mice fed the high-fructose diet and LGG.
Conclusions:
We show for the first time that LGG protects mice from NAFLD induced by a high-fructose diet. The underlying mechanisms of protection likely involve an increase of beneficial bacteria, restoration of gut barrier function and subsequent attenuation of liver inflammation and steatosis.
Researcher(s):
Honda K et al.
Research Unit(s):
Faculty of Human Ecology, Wayo Women’s University, Chiba, Japan
Takanashi Milk Products Co., Ltd., Technical Research Laboratory, Yokohama, Japan
Title of research:
Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice.
Scientific/Medical Publication:
J Clin Biochem Nutr 2012;51(2):96-101
Reference:
https://www.jstage.jst.go.jp/article/jcbn/51/2/51_11-07/_article
Abstract/Summary:
The antidiabetic effects of lactic acid bacteria were investigated using mice. In Experiment 1, normal ICR mice were loaded with sucrose or starch with or without viable Lactobacillus rhamnosus GG cells. GG significantly inhibited postprandial blood glucose levels when administered with sucrose or starch. In Experiment 2, KK-Ay mice, a model of genetic type 2 diabetes, were given a basal diet containing viable GG cells or viable Lactobacillus delbrueckii subsp. bulgaricus cells for 6 weeks. Viable GG cells significantly inhibited fasting blood glucose, postprandial blood glucose in a glucose tolerance test and HbA1c. Such effects were not shown by viable L. bulgaricus cells. In Experiment 3, the KK-Ay mice were given a basal diet containing viable GG cells or heat-treated GG cells for 3 weeks. The viable GG cells significantly suppressed fasting blood glucose and impaired glucose tolerance, but the heat-treated GG showed no effects. These results demonstrated that GG decreased the postprandial blood glucose in ICR mice, and that the antidiabetic activity of lactic acid bacteria on the KK-Ay mice differed depending on the bacterial strain and whether the bacterium is viable when it arrives in the intestine. In the present study, we conclude that the antidiabetic activity may result from continuous inhibition of the postprandial blood glucose through suppression of glucose absorption from the intestine. These findings indicate that specific strains of lactic acid bacterium can be expected to be beneficial for the management of type 2 diabetes.
Researcher(s):
El-Nezami H et al.
Research Unit(s):
Key Centre for Applied and Nutritional Toxicology, RMIT-University, Melbourne, Vic 3001, Australia
Department of Biochemistry and Food Chemistry, Turku University, Turku, Finland
Title of research:
Ability of diary strains of lactic acid bacteria to bind common food carcinogen, Aflatoxin B1.
Scientific/Medical Publication:
Food Chem Toxicol 1998(36);321-6
Reference:
http://www.sciencedirect.com/science/article/pii/S0278691597001609
Abstract/Summary:
This study was conducted to examine the ability of selected dairy strains of lactic acid bacteria to remove aflatoxin B1 (AFB1) from liquid media. Both Lactobacillus rhamnosus strain GG (LBGG) and L. rhamnosus strain LC-705 (LC705) can significantly (P>0.05) remove AFB1 when compared with that by other strains of either Gram-positive or Gram-negative bacteria. Removal of AFB1 by LBGG and LC705 was a rapid process with approximately 80% AFB1 removed at 0 hr. Removal of AFB1 by these two strains was both temperature and bacterial concentration dependent.
Researcher(s):
Haskard C et al.
Research Unit(s):
Key Centre for Applied and Nutritional Toxicology, RMIT-University, Melbourne, Victoria 3001, Australia
Title of research:
Factors affecting the sequestration of aflatoxin by Lactobacillus rhamnosus strain GG.
Scientific/Medical Publication:
Chemico-Biological Interactions 2000;128:39-49
Reference:
http://www.sciencedirect.com/science/article/pii/S0009279700001861
Abstract/Summary:
The interaction of a potent carcinogen, aflatoxin B1 (AFB1), with a probiotic strain of lactic acid bacteria, Lactobacillus rhamnosus strain GG (GG), has been investigated. The binding of AFB1 to GG in the late exponential–early stationary phase was studied for viable, heat-killed and acid-killed bacteria. In general, viable, heat-killed and acid-killed GG responded in a similar manner. The effects of pronase E, lipase and m-periodate on AFB1 binding and release were consistent with AFB1 binding predominantly to carbohydrate components of the bacteria. The effect of urea suggested hydrophobic interactions play a major role in binding. Increasing concentration (0.01–1 M) of NaCl or CaCl2 had minor effects on AFB1 binding suggesting some involvement of electrostatic interactions. An increase in pH from 2.5 to 8.5 had no effect on AFB1 binding but decreased binding of AFB2a, possibly due to hydrogen bonding interactions.
Researcher(s):
Lahtinen SJ et al.
Research Unit(s):
Key Centre for Applied and Nutritional Toxicology, RMIT-University, Melbourne, Vic 3001, Australia
Department of Biochemistry and Food Chemistry, University of Turku Vatselankatu 2, Turku, Finland
Title of research:
Binding of aflatoxin B1 to cell wall components of Lactobacillus rhamnosus GG.
Scientific/Medical Publication:
Food Addit Contam 2004;21(2):158-164
Reference:
http://www.ingentaconnect.com/content/tandf/tfac/2004/00000021/00000002/art00006
Abstract/Summary:
The surface of Lactobacillus rhamnosus strain GG (LGG) has previously been shown to bind aflatoxin B1 (AFB1) effectively, it being a food-borne carcinogen produced by certain species of Aspergillus fungi. To establish which components of the cell envelope are involved in the AFB1 binding process, exopolysaccharides and a cell wall isolate containing peptidoglycan were extracted from LGG and its AFB1 binding properties were tested. LGG was also subjected to various enzymatic and chemical treatments and their effects on the binding of AFB1 by LGG were examined. No evidence was found for exopolysaccharides, cell wall proteins, Ca2+ or Mg2+ being involved in AFB1 binding. The AFB1 binding activity of the cell wall isolate indicates that AFB1 binds to the cell wall peptidoglycan of LGG or compounds tightly associated with the peptidoglycan.
Researcher(s):
Gratz S et al
Research Unit(s):
Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
Food and Health Research Centre, University of Kuopio, Kuopio, Finland
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, LIGHT Laboratories, University of Leeds, LS2 9JT Leeds, United Kingdom
Title of research:
Lactobacillus rhamnosus strain GG reduces aflatoxin B1 transport, metabolism and toxicity in Caco-2 cells.
Scientific/Medical Publication:
Appl Eniron Microbiol 2007;73:3958-64
Reference:
http://aem.asm.org/content/73/12/3958.long
Abstract/Summary:
The probiotic Lactobacillus rhamnosus GG is able to bind the potent hepatocarcinogen aflatoxin B1 (AFB1) and thus potentially restrict its rapid absorption from the intestine. In this study we investigated the potential of GG to reduce AFB1 availability in vitro in Caco-2 cells adapted to express cytochrome P-450 (CYP) 3A4, such that both transport and toxicity could be assessed. Caco-2 cells were grown as confluent monolayers on transmembrane filters for 21 days prior to all studies. AFB1 levels in culture medium were measured by high-performance liquid chromatography. In CYP 3A4-induced monolayers, AFB1 transport from the apical to the basolateral chamber was reduced from 11.1% ± 1.9% to 6.4% ± 2.5% (P = 0.019) and to 3.3% ± 1.8% (P = 0.002) within the first hour in monolayers coincubated with GG (1 × 1010 and 5 × 1010 CFU/ml, respectively). GG (1 × 1010 and 5 × 1010 CFU/ml) bound 40.1% ± 8.3% and 61.0% ± 6.0% of added AFB1 after 1 h, respectively. AFB1 caused significant reductions of 30.1% (P = 0.01), 49.4% (P = 0.004), and 64.4% (P < 0.001) in transepithelial resistance after 24, 48, and 72 h, respectively. Coincubation with 1 × 1010 CFU/ml GG after 24 h protected against AFB1-induced reductions in transepithelial resistance at both 24 h (P = 0.002) and 48 h (P = 0.04). DNA fragmentation was apparent in cells treated only with AFB1 cells but not in cells coincubated with either 1 × 1010 or 5 × 1010 CFU/ml GG. GG reduced AFB1 uptake and protected against both membrane and DNA damage in the Caco-2 model. These data are suggestive of a beneficial role of GG against dietary exposure to aflatoxin.
Researcher(s):
El-Nezami H et al.
Research Unit(s):
Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
Food and Health Research Center, University of Kuopio, FIN-70211 Kuopio
Department of Biochemistry and Food Chemistry, University of Turku, FIN-20014 Turku, Finland
Title of research:
Binding rather than metabolism may explain the interaction of two food-grade Lactobacillus strains with zearalenone and its derivative ά-zearalenol.
Scientific/Medical Publication:
Appl Environ Microbiol 2002;68(7):3545-49
Reference:
http://aem.asm.org/content/68/7/3545.long
Abstract/Summary:
The interaction between two Fusarium mycotoxins, zearalenone (ZEN) and its derivative ά-zearalenol (ά-ZOL), with two food-grade strains of Lactobacillus was investigated. The mycotoxins (2 μg ml−1) were incubated with either Lactobacillus rhamnosus strain GG or L. rhamnosus strain LC705. A considerable proportion (38 to 46%) of both toxins was recovered from the bacterial pellet, and no degradation products of ZEN and ά-ZOL were detected in the high-performance liquid chromatograms of the supernatant of the culturing media and the methanol extract of the pellet. Both heat-treated and acid-treated bacteria were capable of removing the toxins, indicating that binding, not metabolism, is the mechanism by which the toxins are removed from the media. Binding of ZEN or ά-ZOL by lyophilized L. rhamnosus GG and L. rhamnosus LC705 was a rapid reaction: approximately 55% of the toxins were bound instantly after mixing with the bacteria. Binding was dependent on the bacterial concentration, and coincubation of ZEN with ά-ZOL significantly affected the percentage of the toxin bound, indicating that these toxins may share the same binding site on the bacterial surface. These results can be exploited in developing a new approach for detoxification of mycotoxins from foods and feeds.
Researcher(s):
Meriluoto J et al.
Research Unit(s):
Department of Biochemistry and Pharmacy, Åbo Akademi University, Tykistökatu 6A,Turku, Finland
Functional Foods Forum, University of Turku, 20014 Turku, Finland
Australian Water Quality Centre, Salisbury SA 5108, Australia
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
Title of research:
Removal of the cyanobacterial toxin microcystin-LR by human probiotics.
Scientific/Medical Publication:
Toxicon 2005;46:111-114
Reference:
http://www.sciencedirect.com/science/article/pii/S0041010105001200
Abstract/Summary:
Three human probiotics, Lactobacillus rhamnosus strains GG and LC-705, and Bifidobacterium lactis strain Bb12, were found to bind the cyanobacterial peptide toxin microcystin-LR from water solutions. The highest removal percentage was 46%, observed with heat-treated L. rhamnosus strain GG (1010 cells/ml) and a microcystin-LR concentration of 0.5 μg/ml during an incubation of 7 h at 35 °C.
Researcher(s):
Nybom SMK et al.
Research Unit(s):
Department of Biochemistry and Pharmacy, Åbo Akademi University, Turku, Finland
Functional Foods Forum, University of Turku, Turku, Finland
Title of research:
Removal of microcystin-LR by strains of metabolically active probiotic bacteria.
Scientific/Medical Publication:
FEMS Microbiol Lett 2007;270(1):27-33
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2007.00644.x/abstract;jsessionid=2F6FF
569B01483839E8D59A11D33E360.f04t02/abstract;jsessionid=2F6FF569B01483839E8D59A11D33E360.f04t02
Abstract/Summary:
The ability of specific strains of probiotic bacteria to remove the cyanobacterial peptide toxin microcystin-LR from aqueous solutions was assessed. Lactobacillus rhamnosus strains GG and LC-705, Bifidobacterium longum 46, Bifidobacterium lactis 420 and Bifidobacterium lactis Bb12 were shown to be the most effective in toxin removal among 11 tested strains. The highest removal percentage of microcystin-LR was 58.1%, observed with B. lactis Bb12 (toxin concentration 100 μg L−1, 1010 CFU mL−1, 37°C, 24 h). Freshly cultured bacteria were shown to be more efficient in microcystin removal than lyophilized or nonviable bacteria. Removal of microcystin-LR was shown to be dependent on both temperature and bacterial concentration. It is concluded that some of the tested strains have good potential in removing microcystins from aqueous solutions.
Researcher(s):
Halttunen T et al.
Research Unit(s):
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
Title of research:
Cadmium removal by Lactic Acid Bacteria.
Scientific/Medical Publication:
Bioscience Microflora 2003；22（3）：93-97
Reference:
http://cat.inist.fr/?aModele=afficheN&cpsidt=15111253
Abstract/Summary:
Diet is the major source of cadmium for the non-smoking population. Currently, no method is available to remove cadmium from food products. Because the content of cadmium in the food is likely to continue to rise in the future, a new method for decontaminating foods is urgently needed. We assessed the ability of safe food grade lactic acid bacteria (LAB) to remove cadmium from an aqueous solution. At a concentration of 10 μg/l up to 70% could be removed within 5 min, and up to 90% after 1 hr. At a concentration of 1000 μg/l between 5 and 30% was removed after 5 min and between 20 ad 55% after 1 hr. Heat-treatment of the bacteria significantly enhanced the removal of Cd at 10 and 100 μg/l, but not at 1000 μg/l. Increased temperature (37°C), prolonged incubation (24 hr) and higher bacterial concentrations (5 x 109 bacteria/ml) were found to increase the removal of Cd. LAB were shown to remove cadmium in a strain, temperature and concentration dependent manner. The results indicate that food grade LAB may provide a much needed means for decontamination of liquid foods. The practical feasibility of this approach deserves to be further investigated considering the importance of Cd removal from food.
Researcher(s):
Lee YK et al.
Research Unit(s):
Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore 117597
Department of Clinical Nutrition; Food and Health Research Centre, Mediteknia, University of Kuopio, FIN-70211 Kuopio, Finland
Australian Water Quality Centre, Private Mail Bag 3, Salisbury, South Australia 5108, Australia
Department of Clinical Nutrition, Mediteknia, University of Kuopio, P Kuopio, Finland
Department of Biochemistry and Food Chemistry, Vatselankatu 2, 20014-University of Turku, Turku, Finland
Title of research:
Kinetics of adsorption and desorption of aflatoxin B1 by viable and nonviable bacteria.
Scientific/Medical Publication:
J Food Prot 2003;666(3):426-30
Reference:
Abstract/Summary:
The reactions involved in the binding (adsorption) and release (desorption) of aflatoxin B1 (AFB1) to and from the surface of bacteria were investigated. Viable and heat-killed Lactobacillus rhamnosus GG, L. rhamnosus LC-705, and Propionibacterium freudenreichii subsp. shermanii JS were incubated in phosphate-buffered saline containing variable concentrations (0.0017 to 13.3 μg/ml) of AFB1. The relationship between the bacterial surface hydrophobicity and the AFB1 adsorption affinity was also investigated. A linear relationship was observed between the specific rate of AFB1 adsorption and the AFB1 concentration for all bacteria. The nature of desorption of adsorbed AFB1 was investigated by repetitive aqueous washes. A linear relationship was observed between the natural log value of the concentration of AFB1 adsorbed and the number of washes for all bacteria studied. The desorption constants were strain-dependent and were lower for heat-killed bacteria than for viable bacteria. Heat treatment appears to alter the surface properties of the bacteria rather than expose new adsorption sites. No correlation was found between the hydrophobicity and the AFB1 adsorption affinity.
Researcher(s):
Kankaanpaa P et al.
Research Unit(s):
Department of Biochemistry and Food Chemistry, Vatselankatu 2, 20014-University of Turku, Turku, Finland
Key Centre for Applied and Nutritional Toxicology, Royal Melbourne Institute of Technology (RMIT), Melbourne, Victoria, Australia
Title of research:
Binding of aflatoxin B1 alters the adhesion properties of Lactobacillus rhamnosus strain GG in a Caco-2 model.
Scientific/Medical Publication:
J Food Prot 2000;63(3):412-414
Reference:
http://hub.hku.hk/handle/10722/178689
Abstract/Summary:
Lactic acid bacteria have been previously reported to possess antimycotoxigenic activities both in vitro and in vivo. The objective of this study was to investigate the effect of aflatoxin B1 on adhesion capability of Lactobacillus rhamnosus strain GG using a Caco-2 adhesion model. Removal of aflatoxin B1 by L. rhamnosus strain GG reduced the adhesion capability of this strain from 30% to 5%. It is therefore concluded that aflatoxins may influence the adhesion properties of probiotics able to sequester them, and subsequently these bacteria may reduce the accumulation of aflatoxins in the intestine via increased excretion of an aflatoxin–bacteria complex.
Researcher(s):
Osterlund P et al.
Research Unit(s):
Department of Oncology, Helsinki University Central Hospital, PO Box 180, 00029 HUS Helsinki, Finland
Institute of Biomedicine, University of Helsinki, PO Box 63, FI-00014 Finland
Valio Ltd, R&D, PO Box 30, FI-00039 VALIO, Helsinki, Finland
Department of Internal Medicine, Helsinki University Central Hospital, PO Box 340, FI-00029 Helsinki, Finland
Department of Anaesthesiology, Helsinki University Central Hospital/Jorvi Hospital, Turuntie 150, FI-02740 Espoo, Finland
Title of research:
Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study.
Scientific/Medical Publication:
Br J Cancer 2007;97:1028-1034
Reference:
http://www.nature.com/bjc/journal/v97/n8/full/6603990a.html
Abstract/Summary:
5-Fluorouracil (5-FU)-based chemotherapy is frequently associated with diarrhoea. We compared two 5-FU-based regimens and the effect of Lactobacillus and fibre supplementation on treatment tolerability. Patients diagnosed with colorectal cancer (n=150) were randomly allocated to receive monthly 5-FU and leucovorin bolus injections (the Mayo regimen) or a bimonthly 5-FU bolus plus continuous infusion (the simplified de Gramont regimen) for 24 weeks as postoperative adjuvant therapy. On the basis of random allocation, the study participants did or did not receive Lactobacillus rhamnosus GG supplementation (1–2 × 1010 per day) and fibre (11 g guar gum per day) during chemotherapy. Patients who received Lactobacillus had less grade 3 or 4 diarrhoea (22 vs 37%, P=0.027), reported less abdominal discomfort, needed less hospital care and had fewer chemotherapy dose reductions due to bowel toxicity. No Lactobacillus-related toxicity was detected. Guar gum supplementation had no influence on chemotherapy tolerability. The simplified de Gramont regimen was associated with fewer grade 3 or 4 adverse effects than the Mayo regimen (45 vs 89%), and with less diarrhoea. We conclude that Lactobacillus GG supplementation is well tolerated and may reduce the frequency of severe diarrhoea and abdominal discomfort related to 5-FU-based chemotherapy.
Researcher(s):
Ciorba MA et al.
Research Unit(s):
Departments of Medicine, Washington University Saint Louis, School of Medicine, Saint Louis, Missouri, USA
Departments of Pathology and Immunology, Washington University Saint Louis, School of Medicine, Saint Louis, Missouri, USA
Title of research:
Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner.
Scientific/Medical Publication:
Gut 2011. doi:10.1136/gutjnl-2011-300367
Reference:
http://gut.bmj.com/content/61/6/829.long
Abstract/Summary:
Background :
The small intestinal epithelium is highly sensitive to radiation and is a major site of injury during radiation therapy and environmental overexposure.
Objective :
To examine probiotic bacteria as potential radioprotective agents in the intestine.
Methods:
8-week-old C57BL/6 wild-type or knockout mice were administered probiotic by gavage for 3 days before 12 Gy whole body radiation. The intestine was evaluated for cell-positional apoptosis (6 h) and crypt survival (84 h).
Results :
Gavage of 5×107 Lactobacillus rhamnosus GG (LGG) improved crypt survival about twofold (p<0.01); the effect was observed when administered before, but not after, radiation. Conditioned medium (CM) from LGG improved crypt survival (1.95-fold, p<0.01), and both LGG and LGG-CM reduced epithelial apoptosis particularly at the crypt base (33% to 18%, p<0.01). LGG was detected in the distal ileal contents after the gavage cycle, but did not lead to a detectable shift in bacterial family composition. The reduction in epithelial apoptosis and improved crypt survival offered by LGG was lost in MyD88−/−, TLR-2−/− and cyclo-oxygenase-2−/− (COX-2) mice but not TLR-4−/− mice. LGG administration did not lead to increased jejunal COX-2 mRNA or prostaglandin E2 levels or a change in number of COX-2-expressing cells. However, a location shift was observed in constitutively COX-2-expressing cells of the lamina propria from the villi to a position near the crypt base (villi to crypt ratio 80:20 for control and 62:38 for LGG; p<0.001). Co-staining revealed these COX-2-expressing small intestinal lamina propria cells to be mesenchymal stem cells.
Conclusions :
LGG or its CM reduce radiation-induced epithelial injury and improve crypt survival. A TLR-2/MyD88 signalling mechanism leading to repositioning of constitutive COX-2-expressing mesenchymal stem cells to the crypt base is invoked.
Researcher(s):
Prisciandaro LD et al.
Research Unit(s):
School of Animal and Veterinary Sciences, University of Adelaide (Roseworthy Campus), Roseworthy, South Australia, Australia
Centre for Pediatric and Adolescent Gastroenterology, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, South Australia, Australia
Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
South Australian Research and Development Institute, Adelaide, South Australia, Australia
Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
Pediatric Education and Research Institute, Sansom Institute, University of South Australia, Adelaide, South Australia, Australia
Title of research:
Probiotic factors partially prevent changes to caspases 3 and 7 activation and transepithelial electrical resistance in a model of 5-fluorouracil-induced epithelial cell damage.
Scientific/Medical Publication:
Support Care Cancer 2012;20(12):3205-10
Reference:
http://link.springer.com/article/10.1007%2Fs00520-012-1446-3
Abstract/Summary:
The potential efficacy of a probiotic-based preventative strategy against intestinal mucositis has yet to be investigated in detail. We evaluated supernatants (SN) from Escherichia coli Nissle 1917 (EcN) and Lactobacillus rhamnosus GG (LGG) for their capacity to prevent 5-fluorouracil (5-FU)-induced damage to intestinal epithelial cells. A 5-day study was performed. IEC-6 cells were treated daily from days 0 to 3, with 1 mL of PBS (untreated control), de Man Rogosa Sharpe (MRS) broth, tryptone soy roth (TSB), LGG SN, or EcN SN. With the exception of the untreated control cells, all groups were treated with 5-FU (5 μM) for 24 h at day 3. Transepithelial electrical resistance (TEER) was determined on days 3, 4, and 5, while activation of caspases 3 and 7 was determined on days 4 and 5 to assess apoptosis. Pretreatment with LGG SN increased TEER (p < 0.05) compared to controls at day 3. 5-FU administration reduced TEER compared to untreated cells on days 4 and 5. Pretreatment with MRS, LGG SN, TSB, and EcN SN partially prevented the decrease in TEER induced by 5-FU on day 4, while EcN SN also improved TEER compared to its TSB vehicle control. These differences were also observed at day 5, along with significant improvements in TEER in cells treated with LGG and EcN SN compared to healthy controls. 5-FU increased caspase activity on days 4 and 5 compared to controls. At day 4, cells pretreated with MRS, TSB, LGG SN, or EcN SN all displayed reduced caspase activity compared to 5-FU controls, while both SN groups had significantly lower caspase activity than their respective vehicle controls. Caspase activity in cells pretreated with MRS, LGG SN, and EcN SN was also reduced at day 5, compared to 5-FU controls. We conclude that pretreatment with selected probiotic SN could prevent or inhibit enterocyte apoptosis and loss of intestinal barrier function induced by 5-FU, potentially forming the basis of a preventative treatment modality for mucositis.
Researcher(s):
Verma A et al.
Research Unit(s):
Department of Microbiology , Panjab University , Chandigarh , India
Title of research:
Probiotics Lactobacillus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats.
Scientific/Medical Publication:
Nutr Cancer 2013:65(1):84-91
Reference:
Abstract/Summary:
Diet makes an important contribution to colorectal cancer (CRC) risk implying risks for CRC are potentially reducible. Therefore, the probiotics have been suggested as the prophylactic measure in colon cancer. In this study, different probiotics were used to compare their protective potential against 1,2 dimethylhydrazine dihydrochloride (DMH)-induced chemical colon carcinogenesis in Sprague Dawley rats. Animals belonging to different probiotic groups were fed orally with 1 × 109 lactobacilli daily for 1 week, and then a weekly injection of DMH was given intraperitoneally for 6 wks with daily administration of probiotic. Lactobacillus GG and L.acidophilus + DMH-treated animals had maximum percent reduction in ACF counts. A significant decrease (P < 0.05) in fecal nitroreductase activity was observed in L.casei + DMH and L.plantarum + DMH-treated rats whereas β-glucuronidase activity decreased in L.GG + DMH and L.acidophilus + DMH-treated rats. Animals treated with Bifidobacterium bifidum + DMH had significant decreased β-glucosidase activity. However, not much difference was observed in the colon morphology of animals belonging to various probiotic + DMH-treated rats compared with DMH-treated alone. The results indicated that probiotics, L.GG, and L.acidophilus can be used as the better prophylactic agents for experimental colon carcinogenesis.
Researcher(s):
Wollowski I et al.
Research Unit(s):
Institute for Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany
Department of Molecular Toxicology and Pharmacogenetics, Institute for Nutrition and Environment, Friedrich-Schiller-University Jena, Germany.
Title of research:
Protective role of probiotics and prebiotics in colon cancer.
Scientific/Medical Publication:
Am J Clin Nutr 2001;73(Suppl):451S-455S
Reference:
http://ajcn.nutrition.org/content/73/2/451s.abstract
Abstract/Summary:
Ingestion of viable probiotics or prebiotics is associated with anticarcinogenic effects, one mechanism of which is the detoxification of genotoxins in the gut. This mechanism was shown experimentally in animals with use of the rat colon carcinogen 1,2-dimethylhydrazine and by determining endpoints that range from tumorigenesis to induction of DNA damage. Because of the complexity of cancer initiation, cancer progression, and the exposure of cancer in the gut, many types of interactions may be envisaged. Notably, some of our newer studies showed that short-lived metabolite mixtures isolated from milk that was fermented with strains of Lactobacillus bulgaricus and Streptococcus thermophilus are more effective in deactivating etiologic risk factors of colon carcinogenesis than are cellular components of microorganisms. Ingestion of prebiotics results in a different spectrum of fermentation products, including the production of high concentrations of short-chain fatty acids. Gut flora, especially after the ingestion of resistant starch, induces the chemopreventive enzyme glutathione transferase π in the colon of the rat. Together, these factors lead to a reduced load of genotoxic agents in the gut and to an increased production of agents that deactivate toxic components. Butyrate is one such protective agent and is associated with lowering cancer risk. It was recently shown that buytrate may inhibit the genotoxic activity of nitrosamides and hydrogen peroxide in human colon cells. In humans, the ingestion of probiotics leads to the excretion of urine with low concentrations of components that are genotoxic in human colon cells and high concentrations of components that induce oxidized DNA bases.
Researcher(s):
Lim BK et al.
Research Unit(s):
Department of Microbiology, National University of Singapore, Singapore
Department of Surgery, National University of Singapore, Singapore
Department of Anatomy, National University of Singapore, Singapore
Title of research:
Chemopreventive effect of Lactobacillus rhamnosus on growth of a subcutaneously implanted bladder cancer cell line in the mouse.
Scientific/Medical Publication:
Jpn J Cancer Res 2002;93:36-41
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2002.tb01198.x/full
Abstract/Summary:
Lactic acid bacteria are known to have beneficial effects on the host, such as preventing carcinogenesis. The present study was designed to evaluate the chemopreventive effects of Lactobacttlus rhamnosus strain GG (LGG) in suppressing bladder cancer formation in a murine subcutaneous model of bladder cancer involving the inoculation of MB49 cells in C57B/L6 mice. After tumor implantation, one group of mice (n=8) was fed LGG immediately. The remaining mice that had tumors between 0.03–0.1 cm3 were divided into two groups: those fed LGG after 7 days (n=7) and those fed saline (n=7). A second group of mice without any inoculation of MB49 cells was fed either LGG (n=10) or saline (n=10) and served as non-tumor-bearing controls. LGG was administered orally at 1.6×l08 colony-forming units daily. Mice fed LGG immediately after tumor cell implantation formed smaller tumors and some did not develop tumors (2 out of 8 mice), when the tumor burden was small. The level of spleen CD3, CD4 and CD8a T lymphocytes, as well as natural killer cells in mice fed immediately with LGG was also higher than that in control tumor-bearing mice. There was an increase in lymphocytes and granulocytes in tumor sections, especially from the immediately fed group as compared to the controls. Our results suggest that oral consumption of LGG may prevent tumor growth via modulation of the immune system. The potential of LGG as an adjunct therapy in the treatment of bladder cancer could be further explored.
Researcher(s):
Roller M et al.
Research Unit(s):
Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Haid-und-Neu-Str. 9, Karlsruhe, Germany
Department of Pharmacology, University of Florence, 6 Viale Pieraccini, Florence, Italy
Title of research:
Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis.
Scientific/Medical Publication:
Br J Nutr 2004;92:931-938
Reference:
Abstract/Summary:
Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0·01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0·01) and in MLN of rats not treated with AOM (P<0·05). Interferon-γ production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0·05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0·01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.
Researcher(s):
Seow SW et al.
Research Unit(s):
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore,
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore
Title of research:
Expression of chemokine/cytokine genes and immune cell recruitment following the instillation of Mycobacterium bovis, bacillus Calmette-Guerin or Lactobacillus rhamnosus strain GG in the healthy murine bladder.
Scientific/Medical Publication:
Immunology 2008;124(3):419-27
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440836/
Abstract/Summary
Mycobacterium bovis, bacillus Calmette–Guérin (BCG) is the current gold standard for bladder cancer therapy. In this study a profile of the gene expression changes that occur after BCG instillation in the bladders of healthy mice was produced and compared to the type of immune cells recruited into the bladder. A similar comparison was made for Lactobacillus rhamnosus strain GG (LGG) instillations in healthy mice to determine its potential in the immunotherapy of bladder cancer. Mice were given six weekly instillations and were killed after the fourth, fifth and sixth instillations of BCG or LGG. Their bladders were harvested for chemokine/cytokine messenger RNA analysis using an array as well as semi-quantitative reverse transcription–polymerase chain reaction. In a second set of mice both the bladder and draining lymph nodes were harvested for the analysis of immune cells. BCG significantly upregulated genes for T helper type 1 (Th1) chemokines: Cxcl2, Cxcl9, Cxcl10, Xcl1; and increased the expression of Th1/Th2 chemokines: RANTES, Ccl6 and Ccl7; Th1 polarizing cytokines: Il1β and Tnfa; and Fcγr1 and iNOS as early as after four weekly instillations. Most of these genes remained highly expressed after 6 weeks. In contrast, LGG transiently induced Cxcl10, Il16, Fcεr1 and Il1r2. Despite these findings, LGG instillation induced the recruitment of natural killer cells into the bladder and draining lymph nodes, as was observed for BCG instillation.
Researcher(s):
Yan F et al.
Research Unit(s):
Departments of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Departments of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
Department of Pathology, University of Washington School of Medicine, Seattle, Washington,USA
Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, Pennsylvania, USA
Departments of Pediatrics and Biochemistry and Molecular Biology, University of Southern California, USA
Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California, USA
Title of research:
A Lactobacillus rhamnosus GG-derived soluble protein, p40,stimulates ligand release from intestinal epithelial cells to transactivate Epidermal Growth Factor receptor.
Scientific/Medical Publication:
J Biol Chem 2013;288(42):30742-30751
Reference:
http://www.jbc.org/content/288/42/30742.abstract
Abstract/Summary:
Background:
p40 is a Lactobacillus rhamnosus GG-derived protein.
Results:
p40 stimulates ADAM17 activation and HB-EGF release, which is required for EGF receptor transactivation, prevention of apoptosis, and preservation of barrier function in intestinal epithelial cells.
Conclusion:
p40 transactivates the EGF receptor through ADAM17-mediated HB-EGF release in intestinal epithelial cells.
Significance:
These results define a mechanism of p40 in modulating intestinal epithelial cell homeostasis.
Researcher(s):
Dong MY et al.
Research Unit(s):
Department of Community Health, Tufts University School of Medicine Boston, MA, USA
Title of research:
Effects of feeding Lactobacillus GG on lethal irradiation in mice.
Scientific/Medical Publication:
Diagn Microbiol Infect Dis 1987;7:1-7
Reference:
http://www.dmidjournal.com/article/0732-8893(87)90063-0/abstract
Abstract/Summary:
Mice exposed to 1400 rads of total body irradiation experienced 80%–100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls.
Researcher(s):
Tao Y et al.
Research Unit(s):
Section of Infectious Diseases, Department of Medicine, University of Chicago, Chicago, Illinois
Martin Boyer and IBD Research Center, University of Chicago, Chicago, Illinois
Department of Surgery, University of Chicago, Chicago, Illinois
Department of Microbiology, University of Chicago, Chicago, Illinois
Title of research:
Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells.
Scientific/Medical Publication:
Am J Physiol Cell Physiol 2006;290:C1018-30
Reference:
http://ajpcell.physiology.org/content/290/4/C1018.long
Abstract/Summary:
Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce heat shock protein (Hsp) expression in intestinal epithelial cells. LGG-CM induces both Hsp25 and Hsp72 in a time- and concentration-dependent manner. These effects are mediated by a low-molecular-weight peptide that is acid and heat stable. DNA microarray experiments demonstrate that Hsp72 is one of the most highly upregulated genes in response to LGG-CM treatment. Real-time PCR and electrophoretic mobility shift assay confirm that regulation of Hsp induction is at least in part transcriptional in nature, involving heat shock factor-1. Although Hsps are not induced for hours after exposure, transient exposure to LGG-CM is sufficient to initiate the signal for Hsp induction, suggesting that signal transduction pathways may be involved. Experiments confirm that LGG-CM modulates the activity of certain signaling pathways in intestinal epithelial cells by activating MAP kinases. Inhibitors of p38 and JNK block the expression of Hsp72 normally induced by LGG-CM. Functional studies indicate that LGG-CM treatment of gut epithelial cells protects them from oxidant stress, perhaps by preserving cytoskeletal integrity. By inducing the expression of cytoprotective Hsps in gut epithelial cells, and by activating signal transduction pathways, the peptide product(s) secreted by LGG may contribute to the beneficial clinical effects attributed to this probiotic.
Researcher(s):
Donato KA et al.
Research Unit(s):
Cell Biology Program, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Title of research:
Lactobacillus rhamnosus GG attenuates interferon-ɣ and tumor necrosis factor-ɑ-induced barrier dysfunction and pro-inflammatory signalling.
Scientific/Medical Publication:
Microbiology 2010 July 23;doi:10.1099/mic.0.040139-0
Reference:
http://mic.sgmjournals.org/content/156/11/3288.long
Abstract/Summary:
The intestinal epithelium forms a protective barrier against luminal contents and the external environment, mediated via intercellular tight junctions (TJs). The TJ can be disrupted via cell signalling induced by either enteric pathogens or pro-inflammatory cytokines, thereby contributing to various intestinal disorders ranging from acute infectious diarrhoea to chronic inflammatory bowel diseases. Probiotics, such as Lactobacillus rhamnosus GG (LGG), are reported to confer beneficial effects on epithelial cells, including antagonizing infections and reducing overt pro-inflammatory responses, but the underlying mechanisms of these observed effects require further characterization. We hypothesized that probiotics preserve barrier function by interfering with pro-inflammatory cytokine signalling. Caco-2bbe cells were seeded into Transwells to attain polarized monolayers with intercellular TJs. Monolayers were inoculated apically with the probiotic LGG 3 h prior to the addition of IFN-γ (100 ng ml−1) to the basolateral medium overnight. The monolayers were then placed in fresh basal medium±TNF-α (10 ng ml−1) and transepithelial electrical resistance (TER) measurements were taken over the time-course of TNF-α stimulation. To complement the TER findings, cells were processed for zona occludens-1 (ZO-1) immunofluorescence staining. As a measure of TNF-α downstream signalling, cells were immunofluorescently stained for NF-κB p65 subunit and CXCL-8 mRNA was quantified by qRT-PCR. Basal cell culture medium was collected after overnight TNF-α stimulation to measure secreted chemokines, including CXCL-8 (interleukin-8) and CCL-11 (eotaxin). Following LGG inoculation, IFN-γ priming and 24 h TNF-α stimulation, epithelial cells maintained TER and ZO-1 distribution. LGG diminished the nuclear translocation of p65, demonstrated by both immunofluorescence and CXCL-8 mRNA expression. CXCL-8 and CCL-11 protein levels were decreased in LGG-inoculated, cytokine-challenged cells. These findings indicate that LGG alleviates the effects of pro-inflammatory cytokines on epithelial barrier integrity and inflammation, mediated, at least in part, through inhibition of NF-κB signalling.
Researcher(s):
Rafter J et al.
Research Unit(s):
Department of Medical Nutrition, Karolinska Institutet, Huddinge, Sweden
The Mercy University Hospital and Cork Cancer Research Centre, Cork, Ireland
Department of Microbiology and the Department of Medicine, University College Cork, Cork, Ireland
Department of Pharmacology, University of Florence, Florence, Italy
Northern Ireland Centre for Food & Health, University of Ulster, Coleraine, Northern Ireland
Department of Nutritional Toxicology, Friedrich-Schiller University of Jena, Jena, Germany
Department of Food and Nutrition, Technical University of Munich, Munich, Germany
Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Karlsruhe, Germany
University of Hasselt, Hasselt, Belgium
ORAFTI, Tienen, Belgium
Title of research:
Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients.
Scientific/Medical Publication:
Am J Clin Nutr 2007;85:488-96
Reference:
http://ajcn.nutrition.org/content/85/2/488.long
Abstract/Summary:
Background:
Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak.
Objective:
The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation—oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)—is able to reduce the risk of colon cancer in humans.
Design:
The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined.
Results:
Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon γ in the cancer patients.
Conclusions:
Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.
Researcher(s):
Seow SW et al.
Research Unit(s):
Departments of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Departments of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Departments of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Title of research:
Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors.
Scientific/Medical Publication:
Cancer Sci 2010;101(3):751-758
Reference:
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2009.01426.x/abstract
Abstract/Summary:
The present gold standard for bladder cancer is Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy. But it has a non-responder rate of 30–50% and side effects are common. Lactobacillus casei strain Shirota has been reported to reduce the incidence of recurrence in bladder cancer patients and to cure tumor-bearing mice. Our aim was to determine if Lactobacillus rhamnosus GG (LGG) could be as efficacious as BCG in a murine model of bladder cancer. MB49 bladder cancer cells secreting human prostate-specific antigen were implanted orthotopically in female C57BL/6 mice and urinary prostate-specific antigen levels were used as a marker of tumor growth. Mice were treated with either live or lyophilized LGG given via intravesical instillation, or both oral and intravesical LGG given once a week for a period of 6 weeks starting at day 4 after tumor implantation. A comparison of LGG and BCG immunotherapy was also carried out. LGG therapy (live or lyophilized) significantly (P = 0.006) increased the number of cured mice. Cytokine arrays and immune cell recruitment analysis revealed differences between untreated, treated, cured, and tumor-bearing mice. LGG therapy restored XCL1 levels to those in healthy bladders. LGG also recruited large numbers of neutrophils and macrophages to the tumor site. Intravesical LGG and BCG immunotherapy had cure rates of 89 and 77%, respectively, compared with 20% in untreated mice. LGG has the potential to replace BCG immunotherapy for the treatment of bladder cancer.
Researcher(s):
Commane DM et al.
Research Unit(s):
NICHE, The University of Ulster, Coleraine, Northern Ireland
Title of research:
Effects of fermentation products of pro-and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon.
Scientific/Medical Publication:
Nutr Cancer 2005:51:102-109
Reference:
Abstract/Summary:
Evidence from in vivo and in vitro studies suggests that the consumption of pro- and prebiotics may inhibit colon carcinogenesis; however, the mechanisms involved have, thus far, proved elusive. There are some indications from animal studies that the effects are being exerted during the promotion stage of carcinogenesis. One feature of the promotion stage of colorectal cancer is the disruption of tight junctions, leading to a loss of integrity across the intestinal barrier. We have used the Caco-2 human adenocarcinoma cell line as a model for the intestinal epithelia. Trans-epithelial electrical resistance measurements indicate Caco-2 monolayer integrity, and we recorded changes to this integrity following exposure to the fermentation products of selected probiotics and prebiotics, in the form of nondigestible oligosaccharides (NDOs). Our results indicate that NDOs themselves exert varying, but generally minor, effects upon the strength of the tight junctions, whereas the fermentation products of probiotics and NDOs tend to raise tight junction integrity above that of the controls. This effect was bacterial species and oligosaccharide specific. Bifidobacterium Bb 12 was particularly effective, as were the fermentation products of Raftiline and Raftilose. We further investigated the ability of Raftilose fermentations to protect against the negative effects of deoxycholic acid (DCA) upon tight junction integrity. We found protection to be species dependent and dependent upon the presence of the fermentation products in the media at the same time as or after exposure to the DCA. Results suggest that the Raftilose fermentation products may prevent disruption of the intestinal epithelial barrier function during damage by tumor promoters.
Researcher(s):
Kandasamy M et al.
Research Unit(s):
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Title of research:
Lactobacilli secreting a tumor antigen and IL15 activates neutrophils and dendritic cells and generates cytotoxic T lymphocytes against cancer cells.
Scientific/Medical Publication:
Cell Immunol 2011;271(1):89-96
Reference:
http://www.sciencedirect.com/science/article/pii/S0008874911001420
Abstract/Summary:
Lactobacillus rhamnosus GG (LGG) has been used to successfully induce tumor regression in an orthotopic model of bladder cancer. Increased infiltration of neutrophils and macrophages into the tumor mass was observed after therapy. This study evaluates the potential of LGG to induce a directed anti-tumor response. Lactobacilli were modified to secrete the prostate specific antigen (PSA) or IL15 and PSA (IL-15-PSA). Neutrophils and DC were exposed to LGG for 2 h as in clinical therapy for bladder cancer. Recombinant LGG activated neutrophils (elevated MHC class I expression) induced DC maturation (increased expression of CD86, CD80, CD40, MHC II and CD83), T cell proliferation and PSA specific cytotoxic T lymphocytes (CTL) activity. IL15 enhanced direct DC activation of CTL. Thus LGG secreting tumor antigens may activate antigen specific immune responses when instilled intravesically and IL15 could enhance this response.
Researcher(s):
Goldin et al.
Research Unit(s):
Department of Family Medicine and Community Health , Tufts University School of Medicine , 136 Harrison Ave., Boston, MA, USA
Department of Family Medicine and Community Health , Tufts University School of Medicine , Boston, MA, USA
Department of Pathology , Tufts University School of Veterinary Medicine , Boston, MA, USA
Title of research:
The effect of Lactobacillus GG on the initiation and promotion of DMH-induced intestinal tumors in the rat.
Scientific/Medical Publication:
Nutr Cancer 1996; 25:197-204
Reference:
Abstract/Summary:
Male Fischer 344 rats were fed a 20% or a 5% corn oil diet and were injected subcutaneously with dimethylhydrazine (DMH) weekly for 16 weeks. In addition, an approximately equal number of animals challenged with DMH were fed daily, until the end of the study, 2 × 1010 Lactobacillus casei subsp. rhamnosus strain GG starting three weeks before DMH administration or after the ninth weekly injection. The feeding of the Lactobacillus GG before and during carcinogen treatment resulted in a significant decrease in the incidence of colon tumors and the number of small intestinal and colon tumors per tumor‐bearing animal for rats fed a 20% corn oil diet. This decrease in tumor incidence or number of tumors was not seen when animals were fed the Lactobacillus after the ninth week of carcinogen treatment. Animals fed a 5% corn oil diet had a lower tumor incidence and number of tumors resulting from the decrease in dietary fat; in addition the feeding of Lactobacillus GG before the carcinogen challenge resulted in a lower incidence of colon tumors. These studies show that a specific strain of L. casei subsp. rhamnosus designated GG can interfere with the initiation or early promotional stages of DMH‐induced intestinal tumorigenesis, and this effect is most pronounced for animals fed a high‐fat diet.
Researcher(s):
Di Caro S et al.
Research Unit(s):
Department of Gastroenterology, Catholic University of Rome, Largo Gemelli 1, Rome, Italy
Department of Pathology, University of Pittsburgh Medical Centre, PA, USA
Title of research:
Effects of Lactobacillus GG on genes expression pattern in a small bowel mucosa.
Scientific/Medical Publication:
Dig Liver Dis 2005;37:320-29
Reference:
http://www.sciencedirect.com/science/article/pii/S1590865805000095
Abstract/Summary:
Background and aims:
Probiotics have been used for cure and prevention of several clinical conditions. However, further insights into the mechanism of action are needed to understand the rationale of their use. The aim of this study was to investigate the influence of Lactobacillus GG on the genetic expression patterns in the small bowel mucosa.
Methods:
Six male patients (38 ± 5 years) with endoscopically proven oesophagitis were enrolled. All patients were treated for 1 month with esomeprazole and randomised to receive Lactobacillus GG or placebo. After 1 month of treatment, upper endoscopy was repeated. Biopsies of the duodenal mucosa were taken prior to and after the treatment, and the genes expression patterns were assessed using GeneChip Human U133A array. Genes with significant expression changes were selected and analysed to identify specific cellular pathways modified by Lactobacillus GG. To support the array data, 10 target genes were studied using Syber-Green PCR.
Results:
Microarray analysis showed that Lactobacillus GG administration determined the up- and down-regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the reliability of the analysis. Lactobacillus GG mainly affected the expression of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell growth and cell differentiation (cyclins and caspases, oncogenes), cell–cell signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription and transduction.
Conclusions:
These data indicate that administration of Lactobacillus GG is associated with a complex genetic response of the duodenal mucosa, reflected by the up- and down-regulation of several genes involved in specific cellular pathways.
Researcher(s):
Yan F et al.
Research Unit(s):
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee USA
Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
Title of research:
Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth.
Scientific/Medical Publication:
Gastroenterology 2007;132:562-75
Reference:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036990/
Abstract/Summary:
Background & Aims:
Increased inflammatory cytokine levels and intestinal epithelial cell apoptosis leading to disruption of epithelial integrity are major pathologic factors in inflammatory bowel diseases. The probiotic bacterium Lactobacillus rhamnosus GG (LGG) and factors recovered from LGG broth culture supernatant (LGG-s) prevent cytokine-induced apoptosis in human and mouse intestinal epithelial cells by regulating signaling pathways. Here, we purify and characterize 2 secreted LGG proteins that regulate intestinal epithelial cell antiapoptotic and proliferation responses.
Methods :
LGG proteins were purified from LGG-s, analyzed, and used to generate polyclonal antibodies for immunodepletion of respective proteins from LGG-conditioned cell culture media (CM). Mouse colon epithelial cells and cultured colon explants were treated with purified proteins in the absence or presence of tumor necrosis factor (TNF). Akt activation, proliferation, tissue injury, apoptosis, and caspase-3 activation were determined.
Results :
We purified 2 novel proteins, p75 (75 kilodaltons) and p40 (40 kilodaltons), from LGG-s. Each of these purified protein preparations activated Akt, inhibited cytokine-induced epithelial cell apoptosis, and promoted cell growth in human and mouse colon epithelial cells and cultured mouse colon explants. TNF-induced colon epithelial damage was significantly reduced by p75 and p40. Immunodepletion of p75 and p40 from LGG-CM reversed LGG-CM activation of Akt and its inhibitory effects on cytokine-induced apoptosis and loss of intestinal epithelial cells.
Conclusions :
p75 and p40 are the first probiotic bacterial proteins demonstrated to promote intestinal epithelial homeostasis through specific signaling pathways. These findings suggest that probiotic bacterial components may be useful for preventing cytokine-mediated gastrointestinal diseases.
Researcher(s):
Rautava S et al.
Research Unit(s):
Department of Paediatrics, University of Turku. Turku, Finland
Title of research:
Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant.
Scientific/Medical Publication:
J Allergy Clin Immunol 2002;109:119-121
Reference:
http://www.jacionline.org/article/S0091-6749(02)25194-5/abstract
Abstract/Summary:
The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor β2 (TGF-β2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P = .018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P = .0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life.
