Systematic review: effect of probiotics on antibiotic-induced microbiome disruption.

The effectiveness of probiotics in preventing or reversing antibiotic-induced microbiome disruption remains uncertain, and claims of microbiome restoration to its pre-antibiotic state may be overestimated. In this review, we aimed to assess the efficacy of probiotics in preventing or ameliorating disruptions in microbiome composition and function induced by antibiotic treatment. We searched Medline, Embase, and CENTRAL for randomised controlled and non-randomised trials. Participants were individuals of any age who were on systemic antibiotics with a low risk of baseline dysbiosis. The intervention consisted of probiotics during or after antibiotic treatment, compared to placebo, alternative interventions, or no intervention. Outcomes included microbiome composition and diversity analysed using high-throughput molecular methods, alongside microbial function and resistome assessments. Seven studies, reported in eight papers, were reviewed. One study showed probiotics counteracting antibiotic-induced diversity changes, another showed exacerbation of these changes, and four others showed no effect. Effects on taxa abundance ranged from mitigating dysbiosis to selective modulation, no effect, or delayed recovery. One study observed no impact on the resistome, while another reported an increase in antibiotic resistance genes. In conclusion, heterogeneous results preclude a definitive conclusion on the effectiveness of any specific probiotic in restoring antibiotic-exposed microbiomes. For a clearer understanding, future research should be more standardised and long-term, employing advanced methods, such as 16S rRNA gene sequencing and metagenomic sequencing. These studies should strive to include larger, diverse populations to enhance generalisability and clearly define what constitutes a healthy microbiome. Finally, linking changes in the microbiome to specific clinical outcomes is essential for clinical decision making. PROSPERO registration number: CRD42023446214.

Symptoms and management of cow's milk allergy: perception and evidence.

Introduction: The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13). Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results: Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Discussion: Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

Effectiveness and safety of selenium supplementation for type 2 diabetes mellitus in adults: a systematic review of randomised controlled trials.

BACKGROUND: The role of selenium (Se) in the management of type 2 diabetes mellitus (T2DM) remains unclear. We systematically assessed the effectiveness and safety of Se supplementation in adults with T2DM. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched up to April 2018 for randomised controlled trials (RCTs) evaluating the effectiveness of Se against a comparator on DM-related outcomes. RESULTS: Four RCTs (241 participants) were included. In individual RCTs, Se supplementation significantly reduced fasting insulin levels [mean difference (MD) = -3.6 µIU mL-1 ; 95% confidence interval (CI) = -6.36 to -0.84; MD = -5.8 µIU mL-1 ; 95% CI = -9.23 to -2.37], homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (MD = -1; 95% CI = -1.79 to -0.21; MD = -1.6; 95% CI, -2.58 to -0.62) and homeostasis model of assessment-estimated B cell function (HOMA-B) (MD = -13.6; 95% CI = -23.4 to -3.8; MD = -22.6; 95% CI = -36.39 to -8.81). No effects of Se were noted on most of the other outcomes of interest. None of the RCTs assessed the mortality, diabetes-related complications, non-high-density lipoprotein (non-HDL), blood pressure and health-related quality of life. The impact on HDL and fasting plasma glucose (FPG) was ambiguous. Only one adverse event (nausea) was reported as a reason for discontinuing the intervention; however, among the studies, the reporting was not accurate. Furthermore, only one RCT reported increase in FPG level in the Se group (MD = 36.38 mg dL-1 ; 95% CI = 15.39-57.37). CONCLUSIONS: Currently, there is no evidence to support the effectiveness of Se supplementation in the T2DM population.

Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: a randomized clinical trial.

OBJECTIVES: To assess the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of diarrhoea and antibiotic-associated diarrhoea (AAD) in children. METHODS: Hospitalized children who received antibiotics were assigned by a computer-generated list to receive L. reuteri (at 2 × 108 CFU) or placebo, twice daily, for the duration of antibiotic treatment. Follow up was for 1 week after antibiotic cessation. The primary outcome measures were diarrhoea and AAD. Both were defined according to one of three definitions (i) three or more loose or watery stools per day for ≥48 h; (ii) three or more loose or watery stools per day for ≥24 h; or (iii) two or more loose or watery stools per day for ≥24 h. For AAD, it had to be diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea. RESULTS: A total of 250 children were randomized and 247 were analysed (L. reuteri n = 123, placebo n = 124; median age 4 months). The occurrences of diarrhoea and AAD were similar in both groups, regardless of the definition used. Using the strictest definition (i.e. definition (i)), the occurrence of diarrhoea in the L. reuteri group was 25 (20%) compared with 16 (13%) in the placebo group (absolute risk reduction -0.07 (-0.17 to 0.02). The occurrence of AAD was 14 (11.4%) in the L. reuteri group compared with 8 (6.5%) in the placebo group (absolute risk reduction -0.05 (-0.13 to 0.02)). The groups were similar with respect to all secondary outcome measures, including adverse events. CONCLUSIONS: Lactobacillus reuteri was not effective in the prevention of diarrhoea or AAD in children.

Rapid review shows that probiotics and fermented infant formulas do not cause d-lactic acidosis in healthy children.

AIM: Extensive ongoing research on probiotics and infant formulas raises a number of safety questions. One concern is the potential influence of d-lactic acid-containing preparations on the health of infants and children. The aim of this review was to summarise the available knowledge on the ingestion of d-lactic acid-producing bacteria, acidified infant formulas and fermented infant formulas as a potential cause of paediatric d-lactic acidosis. METHODS: A Medline database search was performed in July 2017, with no restrictions on the language, article type or publication date. The 1715 search results were screened for clinical trials, review articles, case series and case reports of relevance to the topic. RESULTS: We identified five randomised controlled trials from 2005 to 2017 covering 544 healthy infants and some case reports and experimental studies. No clinically relevant adverse effects of d-lactic acid-producing probiotics and fermented infant formulas were described in healthy children. However, a harmless, subclinical accumulation of d-lactate was theoretically possible. The only known cases of paediatric d-lactic acidosis occurred in patients with short bowel syndrome or, historically, in infants fed with acidified formulas. CONCLUSION: Our main finding was that probiotics and fermented formulas did not cause d-lactic acidosis in healthy children.

To add or not to add probiotics to infant formulae? An updated systematic review.

We updated evidence on the effects of the administration of probiotic-supplemented infant formulae (IF) compared with unsupplemented IF. Five databases were searched up to September 2016 for randomised controlled trials. Twenty publications were identified, including five new RCTs. Supplementation of IF with Bifidobacterium lactis Bb12, either alone or with Streptococcus thermophilus, had no effect on growth, respiratory illness, antibiotic use, stool frequency or consistency. However, there was a significant reduction in the number of episodes of gastrointestinal infections (Bb12) and a lower frequency of colic or irritability (when both strains were used). Lactobacillus johnsonii La1 had no effect on growth, gastrointestinal infections, or respiratory illness episodes. There were no effects of supplementation of IF with Bifidobacterium longum BL999, alone or with Lactobacillus rhamnosus LPR. L. rhamnosus GG was associated with better growth; it had no effect on colic/crying, or irritability, and it was associated with greater indexes of loose stools and a higher defecation frequency. Lactobacillus reuteri ATCC 55730 had no effect on growth, colic, crying, irritability, respiratory illness, antibiotic use, stool frequency, or stool consistency; however, it reduced the number of episodes of diarrhoea. L. reuteri DSM 17938 had no effect on growth, night-time sleeping, or flatulence, but it reduced the number of spitting episodes. Lactobacillus salivarius CEC5713 had no effect on growth, colic, crying, or irritability; however, it resulted in a significant reduction in the rate of diarrhoea and the number of episodes of respiratory symptoms. In conclusion, the administration of probiotic-supplemented formulae to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some beneficial clinical effects are possible; however, there is no existing robust evidence to recommend their routine use. The latter conclusion may reflect the small amount of data on a specific probiotic strain(s) and outcomes, rather than a genuine lack of an effect.

Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain.

AIM: Lactobacillus reuteri is a Gram-positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP). METHODS: We recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 108 colony-forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks. RESULTS: Both L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p < 0.001). L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded. CONCLUSION: Both L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities.

Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis.

BACKGROUND: Vomiting in children with acute gastroenteritis is a common symptom, and it is considered to be the main cause of failure of oral rehydration therapy. AIM: To systematically update evidence on the effects of ondansetron (5-HT3 serotonin antagonist) for vomiting in children with acute gastroenteritis. METHODS: The Cochrane Library, MEDLINE and EMBASE databases were searched up to April 2016, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. RESULTS: Ten RCTs involving 1215 participants were included. Treatment with ondansetron compared with placebo increased the chance for vomiting cessation up to 1 h after drug administration, relative risk, RR, 1.49 (95% confidence interval 1.17-1.89), but there was no difference between the groups after 4, 24 and 48 h. Treatment with ondansetron compared with placebo reduced the risk of failure of oral rehydration therapy, RR 0.5 (0.37-0.69), increased the intake of oral rehydration solution in 1 h and 4 h, mean difference: 43 mL/1 h (15.5-70.5), and 91 mL/4 h (35-147), respectively, reduced the risk of hospitalisation, RR 0.53 (0.29-0.97), and reduced the need for intravenous rehydration, RR 0.45 (0.31-0.63); however, it had no effect on the need for return visits to the emergency department, RR 1.14 (0.72-1.8). Adverse effects were similar in both groups. CONCLUSIONS: Compared with placebo, ondansetron administration for vomiting in children with acute gastroenteritis can improve the efficacy of oral rehydration therapy.

Cow's milk allergy guidelines: a quality appraisal with the AGREE II instrument.

BACKGROUND: The appropriate diagnosis and management of cow's milk allergy (CMA) is challenging. OBJECTIVE: To systematically review the quality of the existing guidelines on CMA. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched from 2010 to November 2015. The methodological rigour, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. RESULTS: Of the 15 included guidelines, two, both developed by recognized scientific organizations, achieved the highest score (100%). Eight others were considered to be of high quality (i.e., overall quality scores >60%). The quality scores for each domain varied. Of all the domains, clarity and presentation had the highest mean score, and applicability had the lowest mean score. The scores (mean ± SD) for individual domains were as follows: domain 1 (score and purpose) 62 ± 36%; domain 2 (stakeholder involvement) 56 ± 33%; domain 3 (rigor of development) 55 ± 38%; domain 4 (clarity of presentation) 71 ± 29%; domain 5 (applicability) 44 ± 33%; and domain 6 (editorial independence) 60 ± 36%. One guideline had the maximum possible score of 100% for all AGREE II domains. CONCLUSION AND CLINICAL RELEVANCE: A number of guidelines on CMA are available; however, their quality varies. Overall, the guidelines developed by recognized professional/scientific organizations were of the highest quality. These guidelines should be recommended for use. Still, the methodological quality of CMA guidelines may be improved.

Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children.

BACKGROUND: Not all probiotics are equal. AIM: To investigate the efficacy of Lactobacillus reuteri DSM 17938 (L. reuteri) in the management of various types of diarrhoeal diseases in children. METHODS: Medline, Embase, the Cochrane Library, trial registries and reference lists of included studies were searched in January 2016, with no language restriction, for randomised controlled trials (RCTs). RESULTS: Eight RCTs (n = 1229) met the inclusion criteria. In treatment trials, L. reuteri administration reduced the duration of diarrhoea (three RCTs, n = 256, mean difference, MD -24.82 h, 95% CI -38.8 to -10.8) and increased the cure rate on day 1 and day 2. However, heterogeneity and wide confidence intervals call for caution in interpreting results. In preventive trials carried out in hospitalised children, based on the findings from two RCTs (n = 290), there was no significant reduction in the risk of nosocomial diarrhoea, rotavirus diarrhoea or diarrhoea of any origin with L. reuteri administration. Based on one RCT (n = 97), there was no effect of L. reuteri on the risk of antibiotic-associated diarrhoea. However, the evidence is limited because the overall frequency of diarrhoea was surprisingly low. In preventive studies carried out in apparently healthy children, L. reuteri reduced diarrhoeal outcomes in one RCT; the evidence from another trial was less convincing. CONCLUSIONS: In therapeutic settings, L. reuteri administration reduces the duration of diarrhoea and increases the chance of cure. In preventive settings, L. reuteri has the potential to reduce the risk of community-acquired diarrhoea in otherwise healthy children.

Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults.

BACKGROUND: The effects of probiotics are strain specific. The clinical effects of each strain need to be evaluated separately. AIM: To evaluate the efficacy of Lactobacillus rhamnosus GG (LGG) in the prevention of antibiotic-associated diarrhoea (AAD) in children and adults. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up to July 2015, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Twelve RCTs (1499 participants) were included. Treatment with LGG compared with placebo or no additional treatment reduced the risk of AAD in patients treated with antibiotics from 22.4% to 12.3% (11 RCTs, n = 1308, relative risk, RR: 0.49, 95% confidence interval, CI: 0.29-0.83, low QoE). However, when children and adults were evaluated separately, the difference was significant in children only (five RCTs, n = 445, RR 0.48, 95% CI 0.26-0.89; moderate QoE). In adults, the difference was not significant (six RCTs, n = 863, RR 0.48, 95% CI 0.20-1.15; low QoE), except for in a subset of patients receiving antibiotics as part of Helicobacter pylori eradication therapy (four RCTs, n = 280, RR 0.26, 95% CI 0.11-0.59; low QoE). CONCLUSIONS: This meta-analysis shows that Lactobacillus rhamnosus GG is effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. However, the quality of evidence is moderate to low.

Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea.

BACKGROUND: Antibiotic-associated diarrhoea is a common complication of antibiotic use, but it can be prevented with administration of probiotics. AIM: To update our 2005 meta-analysis on the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up until May 2015, with no language restrictions, for randomised controlled trials; additional references were obtained from reviewed articles. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Twenty-one randomised controlled trials (4780 participants), among which 16 were new trials, met the inclusion criteria for this updated systematic review. Administration of S. boulardii compared with placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as defined by the study investigators) in patients treated with antibiotics from 18.7% to 8.5% (risk ratio, RR: 0.47; 95% CI: 0.38-0.57, number needed to treat, NNT: 10; 95% CI: 9-13). In children, S. boulardii reduced the risk from 20.9% to 8.8% (6 randomised controlled trials, n=1653, RR: 0.43, 95% CI: 0.3-0.6); in adults, from 17.4% to 8.2% (15 randomised controlled trials, n=3114, RR: 0.49, 95% CI: 0.38-0.63). Moreover, S. boulardii reduced the risk of Clostridium difficile-associated diarrhoea; however, this reduction was significant only in children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73) and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI: 0.47-1.34). CONCLUSIONS: This meta-analysis confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults.

Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection.

BACKGROUND: Unsatisfactory Helicobacter pylori eradication rates and therapy-associated side effects remain a problem. AIM: To update our 2010 meta-analysis on the effects of Saccharomyces boulardii as supplementation to a standard eradication regimen on H. pylori eradication rates and therapy-associated side effects. METHODS: The Cochrane Library, MEDLINE and EMBASE databases were searched from July 2010 (end date of last search) to February 2015, with no language restrictions, for randomised controlled trials (RCTs); additional references were obtained from reviewed articles. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Eleven RCTs (2200 participants, among them 330 children) met the inclusion criteria. Of the 853 patients in the S. boulardii group, 679 (80%, 95% CI 77-82) experienced eradication compared with 608 of the 855 patients (71%, 95% CI 68-74) in the control group [relative risk (RR) 1.11, 95% confidence interval (CI) 1.06-1.17; moderate quality evidence]. S. boulardii compared with control reduced the risk of overall H. pylori therapy-related adverse effects (RR 0.44, 95% CI 0.31-0.64; moderate quality evidence), particularly of diarrhoea (RR 0.51, 95% CI 0.42-0.62; high quality evidence) and nausea [RR 0.6, 95% CI 0.44-0.83 (moderate quality of evidence)]. CONCLUSIONS: In the populations studied, the effectiveness of standard triple therapy was unsatisfactory. The addition of S. boulardii significantly increased the eradication rate, but it was still below the desired level of success. Saccharomyces boulardii significantly decreased some therapy-related side effects.

Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015.

BACKGROUND: New evidence emerged on early feeding practices and the risk of coeliac disease. AIM: To systematically update evidence on these practices to find out whether there is a need to revise current recommendations. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity. RESULTS: We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development. CONCLUSIONS: Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.

What is new on the term probiotics and the role of probiotics for the management of acute gastroenteritis.

There is an increasing interest in probiotics, and evidence of the effectiveness of probiotics in preventing or treating diarrhoeal diseases is also advancing. The purpose of this short opinion paper is to summarise two aspects of current development in regard to probiotics. First, it discusses what is new with regard to some key questions related to the term 'probiotic'. Second, recent, evidence-based, clinical practice guidelines on the use of probiotics for the management of acute gastroenteritis in children are presented.

Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics

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.

Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain ATCC 55730) for treating acute gastroenteritis in children.

Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical effect in the treatment of acute gastroenteritis (AGE) in children. However, as the L. reuteri ATCC 55730 strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it was replaced by a new strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic resistance. Bioequivalence of the two strains has been suggested. We aimed to systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract books of major scientific meetings were searched in August 2013, with no language restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196) that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L. reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met the inclusion criteria. Compared with placebo or no treatment, DSM 17938 significantly reduced the duration of diarrhoea (mean difference -32 h, 95% confidence interval (CI): -41 to -24) and increased the chance of cure on day 3 (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in hospitalised children, use of both strains of L. reuteri reduced the duration of diarrhoea, and more children were cured within 3 days. Data from outpatients and countryspecific cost-effectiveness analyses are needed. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution.

Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children--updated analysis of randomised controlled trials.

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 ≥10¹° CFU (eight RCTs, n = 1488, MD -1.11 days, 95% CI -1.91 to -0.31) than when used at a daily dose <10¹° 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 (≥10¹° 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.