The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered

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Probiotics and the gut microbiota in intestinal health and disease

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.

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: executive summary.

Background
Probiotics may be effective in reducing the duration of acute infectious diarrhoea.

Objectives
To assess the effects of probiotics in proven or presumed acute infectious diarrhoea.

Search methods
We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review.

Selection criteria
Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent.

Data collection and analysis
Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events.

Main results
We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster‐randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high.

Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta‐analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes.

In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate‐certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low‐certainty evidence).

Effect size was similar and marked heterogeneity persisted in pre‐specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered.

For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD ‐18.03 hours, 95% CI ‐27.28 to ‐8.78, random‐effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants).

No serious adverse events were attributed to probiotics.

Authors' conclusions
Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.

/pdf/probiotics-for-treating-acute-infectious-diarrhoea-4mnx1jqk9h.pdf

Probiotics for treating acute infectious diarrhoea

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.

/pdf/european-society-for-pediatric-gastroenterology-hepatology-5bjcwher3v.pdf

[European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014].

Probiotics are increasingly used for prevention and treatment of diarrhea more in children than in adults. Given the broad spectrum of diarrhea, this review focuses on the main etiologies: acute gastroenteritis, antibiotic-associated diarrhea (AAD), and necrotizing enterocolitis (NEC). For each, we reviewed randomized controlled trials, meta-analyses, and guidelines. For acute gastroenteritis we found 12 guidelines: 5 recommended probiotics and 7 did not. However, the guidelines containing positive recommendations provided proof of evidence from clinical trials and meta-analyses. Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii had the most compelling evidence of efficacy as they reduced the duration of the disease by 1 day. For AAD 4 meta-analyses were found, reporting variable efficacy of probiotics in preventing diarrhea, based on the setting, patient's age, and antibiotics. The most effective strains were LGG and S. boulardii. For NEC, we found 3 randomized controlled trials, 5 meta-analyses, and 4 position papers. Probiotics reduced the risk of NEC enterocolitis and mortality in preterm babies. Guidelines did not support a routine use of probiotics and asked for further data for such sensitive implications. In conclusion, there is strong and solid proof of efficacy of probiotics as active treatment of gastroenteritis in addition to rehydration. There is solid evidence that probiotics have some efficacy in prevention of AAD, but the number needed to treat is an issue. For both etiologies LGG and S. boulardii have the strongest evidence. In NEC the indications are more debated, yet on the basis of available data and their implications, probiotics should be carefully considered.

Probiotics for Prevention and Treatment of Diarrhea.

ummary
Background
Saccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens.

Aim
To assess the effectiveness of S. boulardii in treating acute infectious diarrhoea in children.

Methods
The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included.

Results
Five randomized-controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized-controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was −1.1 days (95% CI: −1.3 to −0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08–0.83; NNT 5, 95% CI: 3–20).

Conclusions
There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies.

/pdf/meta-analysis-saccharomyces-boulardii-for-treating-acute-1sj30fvovi.pdf

Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children

Summary

Background

Vomiting is a common sympton in children with gastroenteritis, but its treatment remains controversial.



Aim

To investigate potential beneficial effects of ondansetron, compared with placebo or no intervention, in treating vomiting during acute gastroenteritis in children.



Methods

The following electronic databases were searched through August 2006: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included.



Results

Four RCTs involving 490 patients with vomiting during acute gastroenteritis were included. Combined data from three RCTs (n = 466) showed that ondansetron compared with the control significantly increased the chance for vomiting cessation soon after drug administration [relative risk (RR): 1.3, 95% confidence interval (CI): 1.2–1.5, number needed to treat (NNT): 5, 95% CI: 4–8], but this effect was not observed at 24 h (three RCTs, n = 144, RR 1.2, 95% CI: 0.9–1.7). Ondansetron significantly reduced the risk of intravenous rehydration (two RCTs, n = 359, RR 0.4, 95% CI: 0.3–0.7, NNT 7, 95% CI: 5–14). Outcome measures not significantly different after ondansetron treatment were the need for hospitalization and return emergency department visits.



Conclusions

Despite some clinical benefits, there is insufficient evidence to recommend the routine use of ondansetron for vomiting during acute gastroenteritis in children.

M. Dylag

Papers

Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children

Meta‐analysis: ondansetron for vomiting in acute gastroenteritis in children