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  • Reduces side-effects of antibiotics
    • The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy.

      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.

    • Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhoea in children with respiratory infections: a randomized study.

      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.

    • Lactobacillus GG and Tributyrin supplementation reduce antibiotic-induced intestinal injury.

      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.

    • Lactobacillus rhamnosus GG intake modifies preschool children’s intestinal microbiota, alleviates penicillin-associated changes, and reduces antibiotic use.

      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.

    • Lactobacillus GG in the prevention of antibiotic-associated diarrhoea in children.

      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.

    • Probiotics in the prevention of antibiotic-associated diarrhea in children: A meta-analysis of randomized controlled trials.

      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.

    • Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy – a placebo-controlled, double-blind randomized pilot study.

      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:

      http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02448.x/abstract;jsessionid=A22B288B0BF917842A15B0EBDE538079.f01t01

       

      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.

    • Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

      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:

      http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004827.pub3/abstract;jsessionid=5CB37E9375AEE7EB300FE3E85F9A6EAE.f03t04

       

      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.

    • Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis.

      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.

  • Reduces the risk of acquiring infections
    • Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: A randomized, placebo-controlled trial.

      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.

    • 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.

      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.

    • Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract 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

      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.

    • Lactobacillus rhamnosus GG Supplementation for Preventing Respiratory Infections in Children: A Meta-analysis of Randomized, Placebo-controlled Trials.

      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.

    • Probiotic prophylaxis of ventilator-associated pneumonia. A blinded, randomized controlled trial.

      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.

    • Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in vitro by the probiotic Lactobacillus rhamnosus GG.

      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 Childrens 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.

    • Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection.

      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.

    • Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.

      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.

    • Lactobacillus rhamnosus GG inhibits invasion of cultured human respiratory cells by prtF1-positive macrolide-resistant group A streptococci.

      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.

    • Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae and beta-hemolytic streptococci).

      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.

    • Effect on long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial.

      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.

    • Probiotics reduce the prevalence of oral Candida in the elderly – a randomized controlled trial.

      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.

    • Long-term safety and impact on infection rates on postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial.

      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.

    • Specific probiotics in reducing the risk of acute infections in infancy - a randomised, double-blind. placebo-controlled study.

      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).

    • Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial.

      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.

    • Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination.

      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.

    • Effect of probiotics on vaccine antibody responses in infancy - a randomized placebo-controlled double-blind trial.

      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.

    • Improved immunogenicity of oral DxRRV reassortant rotavirus vaccine by Lactobacillus casei GG.

      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.

    • Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.

      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

      442787

       

      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.

    • Bovine lactoferrin supplementation for prevention of late-onset sepsis in very-low-birth.weight neonates: a randomized trial.

      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.

    • Effect of Lactobacillus GG supplementation on pulmonary exacerbations in pulmonary exacerbations in patients with cystic fibrosis: A pilot study.

      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.

    • Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity.

      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.

    • Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immmunostimulatory effect in healthy subjects.

      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.

    • Identification of novel proteins secreted by Lactobacillus rhamnosus GG grown in de Mann-Rogosa-Sharpe broth.

      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.

    • Antimicrobial substance from a human Lactobacillus strain.

      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.

    • Probiotic administration reduces mortality and improves intestinal epithelial homeostasis in experimental sepsis.

      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.

    • The Use of the Probiotic Lactobacillus rhamnosus GG and Viral Findings in the Nasopharynx of Children Attending Day Care.

      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.

    • Probiotics for preventing acute upper respiratory tract infections.

      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.

  • Protects against contracting diarrhoea
    • 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.

      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.

    • The management of acute diarrhoea in children. A guide for healthcare professionals. College of Paediatrics

      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:              

      -

    • Enhancement of the circulating antibody secreting cell response in human diarrhea by a human lactobacillus strain.

      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.

    • A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

      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.

    • Lactobacillus GG promotes recovery from acute non-bloody diarrhoea in Pakistan.

      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:                             

      http://journals.lww.com/pidj/Abstract/1995/02000/Lactobacillus_GG_promotes_recovery_from_acute.5.aspx

       

      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.

    • A trial in Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea.

      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.

    • Probiotics for treatment of acute diarrhoea in children - randomised clinical trial of five different preparations.

      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.

    • Lactobacillus GG administered in oral rehydration solution to children with acute diarrhoea: a Multicenter European Trial.

      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:                              

      http://www.researchgate.net/publication/12684789_Lactobacillus_GG_administered_in_oral_rehydration_solution_to_children_with_acute_diarrhea_a_multicenter_European_trial


      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.

    • Effect of oral administration of Lactobacillus GG on the duration of diarrhea and on rotavirus excretion in ambulatory children.

      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:                             

      http://journals.lww.com/jpgn/Fulltext/1997/04000/Effect_of_Oral_Administration_of_Lactobacillus_Gg.88.aspx

       

      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.

    • Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea.

      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.

    • Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillus strain GG.

      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.

    • Oral bacteriotherapy for viral gastroenteritis.

      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. 

    • Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a double-blind, randomized controlled trial.

      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.

    • Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children.

      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.

    • Lactobacillus therapy for acute infectious diarrhea in children : A meta-analysis.

      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.

    • Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine.

      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.

    • Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain GG) against Salmonella typhimurium C5 infection.

      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.

    • Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model.

      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

      Authenticated=false

       

      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.

    • Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.

      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.

    • Lactobacilli and Bifidobacteria Promote Immune Homeostasis by Modulating Innate Immune Responses to Human Rotavirus in Neonatal Gnotobiotic Pigs.

      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.

    • Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in neonatal rats.

      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.

    • Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens.

      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.

    • pH-, lactic acid-, and non-lactic acid-dependent activities of probiotic lactobacilli against Salmonella enterica serovar typhimurium.

      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.

    • The effect of probiotics and organic acids on Shiga-toxin 2 gene expression in enterohemorrhagic Escherichia coli 0157:H7.

      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.

    • Evaluation of antimicrobial activity of probiotic bacteria against Salmonella enterica subsp. enterica serovar Typhimurium 1344 in a common medium under different environmental conditions.

      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.

    • 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.

      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.

    • Lactobacillus rhamnosus GG and Lactobacillus casei suppress Escherichia coli-induced chemokine expression in intestinal epithelial cells.

      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.

    • Evaluation of Lactobacillus rhamnosus GG using an Escherichia coli K88 model of piglet diarrhoea: Effects on diarrhoea incidence, faecal microflora and immune responses.

      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.

    • Salmonella enterica serovar Typhimurium adhesion and cytotoxicity during epithelial cell stress is reduced by Lactobacillus rhamnosus GG.

      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.

    • Lactobacillus rhamnosus GG antagonizes Giardia intestinalis induced oxidative stress and intestinal disaccharidases: an experimental study.

      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.

    • Strong antimicrobial activity of Lactobacillus rhamnosus GG against Salmonella typhimurium is due to accumulation of lactic acid.

      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.

    • Efficacy of probiotic use in acute diarrhea in children- a meta-analysis.

      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.

    • Fecal recovery of a human Lactobacillus strain(ATCC 53103) during dietary therapy of rotavirus diarrhea in infants.

      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.

    • Lactic acid bacteria in the treatment of acute rotavirus 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.

    • Rapid adoption of Lactobacillus rhamnosus GG for acute gastroenteritis.

      Researcher(s):                                 

      Parker MW et al.


      Research Unit(s):                 

      Division of Hospital Medicine, Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, USA

      James M. Anderson Center for Health Systems Excellence, Cincinnati Childrens 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.

    • 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.

      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.

    • Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: A randomized, double-blind, pPlacebo controlled trial.

      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.

    • Management strategies in the treatment of neonatal and paediatric gastroenteritis.

      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.

    • Lactic acid bacteria efficiently protect human and animal intestinal epithelial and immune cells from enteric virus infection.

      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 linevirus 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.

    • Use of Probiotics for Management of Acute Gastroenteritis- A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics.

      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.

    • Review article: the management of acute gastroenteritis in children.

      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:                             

      http://onlinelibrary.wiley.com/doi/10.1111/apt.12163/abstract;jsessionid=9B5CA3971E38E20B0721B2C8DF1653D9.f01t01


      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.

    • 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.

      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.

  • Improves allergic conditions
    • Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

      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.

    • Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immmunostimulatory effect in healthy subjects.

      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.

    • Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy.

      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.

    • Probiotic: a novel approach in the management of food allergy.

      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.

    • Probiotic effects on faecal inflammatory markers and faecal IgA in food allergic atopic eczema/dermatitis syndrome infants.

      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

    • Formula selection for management of children with cow’s milk allergy influences the rate of acquisition of tolerance-a prospective multicenter study.

      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.

    • Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.

      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.

    • Effect of Lactobacillus GG on tolerance acquisition in infants with cow’s milk allergy- A randomized trial.

      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:

      --------

    • Lactobacillus GG effect in increasing IFN-gamma production in infants with cow’s milk allergy.

      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.

    • Induction of inflammation as a possible mechanism of probiotic effect in atopic eczema–dermatitis syndrome.

      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.

    • Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

      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.

    • Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring.

      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.

    • 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.

      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

    • Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats.

      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.

    • Probiotic Lactobacillus rhamnosus downregulates FCER1 and HFH4 expression in human mast cells.

      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.

    • Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG.

      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.

    • Modulation of the maturing gut barrier and microbiota: a novel target in allergic disease.

      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.

    • Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone.

      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.

    • Microflora-associated characteristics in faeces from allergic & nonallergic infants.

      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:                           

      http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2222.2000.00982.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false


      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

    • Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study.

      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.

    • Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.

      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.

    • Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.

      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.

    • Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG-derived enzymes.


      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.


    • Orally administered Lactobacillus gasseri TMC0356 and Lactobacillus GG alleviated nasal blockage of guinea pig with allergic rhinitis.

      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.

    • The role of the intestinal microbiota in the development of atopic disorders.

      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.

    • Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease.

      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.

    • Probiotic bacteria in the management of atopic disease: Underscoring the importance of viability.

      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:                           

      http://journals.lww.com/jpgn/Abstract/2003/02000/Probiotic_Bacteria_in_the_Management_of_Atopic.12.aspx


      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.

    • Ingestion of heat-treated Lactobacillus rhamnosus GG prevents development of atopic dermatitis in NC/Nga mice.

      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.

    • Modulation of the maturing gut barrier and microbiota:a novel target in allergic disease.

      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.

    • Effect of nutrient supplementation on atopic dermatitis in children. A systematic review of probiotics, prebiotics, formula and fatty acids.

      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.

  • Reduces the risk of the newborn baby becoming allergic (primary prevention of allergy)
    • Childhood atopic eczema.

      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.

    • Probiotics in primary prevention of atopic disease:a randomised, placebo-controlled trial.

      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.

    • Probiotics and prevention of atopic disease – a 4-year follow-up of a randomised placebo-controlled trial.

      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.

    • Probiotics during the first 7 years of life: A cumulative risk reduction of eczema in a randomized, placebo-controlled trial.

      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:

      -

    • Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant.

      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.

    • Effect of nutrient supplementation on atopic dermatitis in children. A systematic review of probiotics, prebiotics, formula and fatty acids.

      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.

  • Reduces the risk of tooth decay
    • Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG in milk on dental caries risk in children.

      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.


    • Short-term consumption of probiotic-containing cheese and its effect on dental caries risk factors.

      Researcher(s):                    &nb