If acute diarrhea in children is not treated promptly and effectively, it can lead to severe dehydration and serious sequelae. Due to the imbalance of intestinal bacteria in children with acute diarrhea, the supplementation with probiotics is important, which can improve the intestinal microenvironment, promote immunity, and enhance resistance. This meta-analysis provides further evidence and discussion of the therapeutic effect of probiotics on acute diarrhea in children.

MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched by rapid matching. The input keywords were as follows: (probiotics/synbiotics) and (child/children) and (acute diarrhea/acute gastroenteritis). Articles reporting on randomized controlled trials (RCTs) of probiotics in treating acute diarrhea in children were retrieved. The studies were published from 2010 to 2020. After screening and quality evaluation, Stata 16.0 software was used for the analysis.

Twelve articles with 744 patients were included in the study, and the overall quality of the articles was excellent. Meta-analysis showed that the duration of diarrhea in the probiotics group was shorter than that in the control group [standard mean difference (SMD) =-0.74, 95% CI: -1.11 to -0.37, Z=-3.935, P=0.000], the 2-day treatment efficacy for diarrhea in the probiotics group was greater than that in the control group [odds ratio (OR) =2.12, 95% CI: 1.47-3.05, Z=3.998, P=0.000], and the length of hospital stay in the probiotics group was shorter than that of the control group (SMD =-0.60, 95% CI: -0.74 to -0.47, Z=-8.781, P=0.000). In the subgroup analysis, combined probiotics shortened the duration of diarrhea compared with single probiotic use, and Lactobacillus reuteri and Saccharomyces boulardii had a better therapeutic effect than Lactobacillus rhamnosus or Lactobacillus acidophilus.

In the treatment of acute diarrhea in children, the addition of probiotics can shorten the duration of diarrhea, increase treatment efficacy after 2 days of treatment, and shorten the length of hospital stay. However, because of possible publication bias in the current study, further high-quality RCT studies in clinical settings are needed to verify the current results and continue the exploration of this topic.

Acute diarrhea is a major cause of morbidity and mortality in children under five. Probiotics are beneficial for treating acute diarrhea in children, but unclear which specific probiotic is the most effective. We performed a Bayesian network meta-analysis to examine the comparative effectiveness of probiotics. By searching EMBASE, PubMed, and the Cochrane Library up to 31 March 2021, randomized clinical trials (RCTs) on probiotics for treating acute diarrhea in children were included. Primary outcomes included the duration of diarrhea and diarrhea lasting ≥2 days, and secondary outcomes included the mean stool frequency on day 2 and duration of hospitalization, fever, and vomiting. We assessed the certainty of the evidence of outcomes according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline. Eighty-four studies with twenty-one different interventions in 13,443 children were included. For the primary outcomes, moderate evidence indicated that, Lactobacillus reuteri [mean difference (MD) = -0.84 day; 95% confidence interval (CI), -1.39, -0.29], Bifidobacterium lactis (MD = -0.98 day; 95%CI, -1.82, -0.14), Saccharomyces boulardii (MD = -1.25 day; 95%CI, -1.59, -0.91), Lactobacillus species (spp.) plus Bifidobacterium spp. plus Saccharomyces spp. (MD = -1.19 day; 95%CI, -1.81, -0.58), and Bacillus spp. plus Enterococcus spp. plus Clostridium spp. (MD = -1.1 day; 95%CI, -1.84, -0.35) significantly reduced the duration of diarrhea when compared with placebo. Saccharomyces boulardii [Odds ratio (OR) = 0.22; 95%CI, 0.11, 0.41] and Lactobacillus reuteri (OR = 0.23; 95%CI, 0.090, 0.60) significantly reduced the risk of diarrhea lasting ≥2 days when compared with placebo or no treatment, with moderate evidence. Among all probiotics, Saccharomyces boulardii may be the most effective in reducing both duration of diarrhea (compared with placebo) and risk of diarrhea lasting ≥2 days (compared with placebo or no treatment), with moderate evidence. To be conclusive, Saccharomyces boulardii may be the most effective probiotic for treating acute diarrhea in children, followed by several other single-strain and multi-strain probiotics.

Probiotics may be effective in reducing the duration of acute infectious diarrhoea.

To assess the effects of probiotics in proven or presumed acute infectious diarrhoea.

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.

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.

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.

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.

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.

Since the publication of the 2014 European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Working Group (WG) on Probiotics and Prebiotics guidelines for the management of acute gastroenteritis (AGE), new evidence concerning the efficacy of probiotics has become available. This document provides updated recommendations on the use of probiotics for the treatment of AGE in previously presumed healthy infants and children. A systematic literature search was performed. All pooled analyses were explicitly performed for the current report. The WG graded the recommendations and assessed the certainty of the supporting evidence using the Grading of Recommendations, Assessment Development, and Evaluations tool. The recommendations were formulated if at least 2 randomized controlled trials that used a given probiotic were available. Despite the large number of identified trials, the WG could not identify 2 randomized controlled trial of high quality for any strain that provided benefit when used for treating AGE. The WG made weak recommendations for (in descending order in terms of the number of trials evaluating any given strain): Saccharomyces boulardii (low to very low certainty of evidence); Lactobacillus rhamnosus GG (very low certainty of evidence); L reuteri DSM 17938 (low to very low certainty of evidence); and L rhamnosus 19070-2 and L reuteri DSM 12246 (very low certainty of evidence). The WG made a strong recommendation against L helveticus R0052 and L rhamnosus R0011 (moderate certainty of evidence) and a weak recommendation against Bacillus clausii strains O/C, SIN, N/R, and T (very low certainty of evidence).

Several investigations have found that industry-funded studies tend to inform results favoring the sponsored products. The pressure to demonstrate that a drug or a product causes a favorable outcome may result in investigation biases from industry-funded research. One example of this could be found in the probiotic research funded by the industry. The aim of this study was to assess the effect of industry funding on positive outcomes of the use of probiotics in the management of acute diarrhea. A systematized review of clinical trials on the use of probiotics in the management of acute diarrhea was performed. The associations between the source of funding, clinical outcomes, probiotic genus, and quality of the study were assessed using the χ-test and Fisher's exact test. Sixty-six clinical trials were included; 27 were industry funded, 18 were nonindustry funded, and 21 did not disclose their funding source. There were 48 positive and 30 negative clinical outcomes. There was no significant association between the source of funding and clinical outcomes (P=0.491). No association between the rest of the studied variables and outcomes was observed either (P>0.05). In clinical trials on the use of probiotics in the management of acute diarrhea, the source of funding has no influence on positive clinical outcomes.

Acute infectious diarrhea (AID) is one of the most common diseases in pediatric age with relevant burden both in high- and in low-income countries.Thanks to their direct action on enterocyte functions and indirect actions on mucosal and systemic immune system and intestinal microenvironment, probiotics are an ideal intervention to manage AID in childhood. However, their efficacy is strictly related to strains and indications, and practitioners should take this information into account in clinical practice.This chapter summarizes the main mechanisms of action of probiotics in AID, with a focus on proof of efficacy supporting their use in prevention and treatment of infant AID.The use of selected strains in appropriate doses is strongly recommended by guidelines of AID, based on large and consistent proofs of efficacy and safety. At present, therapy with probiotics of AID is arguably the strongest indication for probiotics in medicine. Future research should investigate probiotic efficacy in at-risk populations and settings where the evidence is missing.Their role in prevention of AID is however questionable in healthy population, whereas it should be considered in at-risk population. Evidence for prevention of diarrhea in day-care centers and communities is lacking, but consistent evidence supports efficacy in prevention of hospital acquired diarrhea.Overall, AID is the most convincing area for probiotic use in children, and effective strains should be used early after onset of symptoms.

Acute diarrhoeal diseases remain a leading cause of global morbidity and mortality particularly among young children in resource-limited countries. Recent large studies utilizing case-control design, prospective sampling and more sensitive and broad diagnostic techniques have shed light on particular pathogens of importance and highlighted the previously under recognized impact of these infections on post-acute illness mortality and growth. Vaccination, particularly against rotavirus, has emerged as a key effective means of preventing significant morbidity and mortality from childhood diarrhoeal disease. Other candidate vaccines against leading diarrhoeal pathogens, such as enterotoxigenic Escherichia coli and Shigella spp., also hold significant promise in further ameliorating the burden of enteric infections in children. Large studies are also currently underway evaluating novel and potential easy-to-implement water, sanitation and hygiene (WASH) preventive strategies. Given the ongoing global burden of this illness, the paucity of new advances in case management over the last several decades remains a challenge. The increasing recognition of post-acute illness mortality and growth impairment has highlighted the need for interventions that go beyond management of dehydration and electrolyte disturbances. The few trials of novel promising interventions such as probiotics have mainly been conducted in high-income settings. Trials of antimicrobials have also been primarily conducted in high-income settings or in travellers from high-income settings. Bloody diarrhoea has been shown to be a poor marker of potentially treatable bacterial enteritis, and rising antimicrobial resistance has also made empiric antimicrobial therapy more challenging in many settings. Novel effective and sustainable interventions and diagnostic strategies are clearly needed to help improve case management. Diarrhoeal disease and other enteric infections remain an unmet challenge in global child health. Most promising recent developments have been focused around preventive measures, in particular vaccination. Further advances in prevention and case management including the possible use of targeted antimicrobial treatment are also required to fully address this critical burden on child health and human potential.

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.

Triggered by the growing knowledge on the link between the intestinal microbiome and human health, the interest in probiotics is ever increasing. The authors aimed to review the recent literature on probiotics, from definitions to clinical benefits, with emphasis on children.

Relevant literature from searches of PubMed, CINAHL, and recent consensus statements were reviewed.

While a balanced microbiome is related to health, an imbalanced microbiome or dysbiosis is related to many health problems both within the gastro-intestinal tract, such as diarrhea and inflammatory bowel disease, and outside the gastro-intestinal tract such as obesity and allergy. In this context, a strict regulation of probiotics with health claims is urgent, because the vast majority of these products are commercialized as food (supplements), claiming health benefits that are often not substantiated with clinically relevant evidence. The major indications of probiotics are in the area of the prevention and treatment of gastro-intestinal related disorders, but more data has become available on extra-intestinal indications. At least two published randomized controlled trials with the commercialized probiotic product in the claimed indication are a minimal condition before a claim can be sustained. Today, Lactobacillus rhamnosus GG and Saccharomyces boulardii are the best-studied strains. Although adverse effects have sporadically been reported, these probiotics can be considered as safe.

Although regulation is improving, more stringent definitions are still required. Evidence of clinical benefit is accumulating, although still missing in many areas. Misuse and use of products that have not been validated constitute potential drawbacks.