Acute gastroenteritis remains one of the most frequent reasons for pediatric consultation and hospitalization worldwide, particularly among children under five and in low- and middle-income countries where limited access to clean water, inadequate sanitation, and lower rotavirus vaccination coverage amplify both incidence and severity. Despite advances in oral rehydration therapy, zinc supplementation, and supportive care, diarrheal diseases continue to impose a heavy clinical and economic burden through increased healthcare utilization, caregiver strain, and impaired child growth and development. The COVID-19 pandemic further disrupted the epidemiology of pediatric gastroenteritis: circulation of major enteric pathogens declined during periods of non-pharmaceutical interventions, then resurged after restrictions eased, before gradually returning toward pre-pandemic patterns in a manner that varied by region and vaccination coverage.

The intestinal microbiota plays a central role in gut homeostasis, immune modulation, and resistance to enteric pathogens. Acute diarrheal episodes are associated with transient but sometimes profound disruptions of microbial composition, which may prolong symptoms, impair intestinal barrier function, and predispose children to recurrence. Probiotics, defined as live microorganisms that confer a health benefit when administered in adequate amounts, have been extensively studied as adjuncts to rehydration in acute infectious diarrhea. However, their effects are strain- and indication-specific, so evidence for one product cannot be extrapolated to another; each strain must be evaluated individually. This principle is precisely why the new review focused on a single, well-characterized strain rather than pooling different probiotic products.

Limosilactobacillus reuteri DSM 17938, formerly classified as Lactobacillus reuteri, is a human-derived strain developed from the parent strain ATCC 55730 by removal of two antibiotic-resistance plasmids. It has demonstrated immunomodulatory activity, antimicrobial effects through the production of reuterin, a broad-spectrum antimicrobial compound that inhibits enteropathogen growth, and supportive actions on epithelial barrier function in both experimental and clinical settings. The strain is among the most extensively studied probiotics in pediatric gastrointestinal disorders and appears, with varying strength, in international and regional guidelines. The World Gastroenterology Organization lists it among probiotics that may reduce the duration of diarrhea in acute gastroenteritis, while the ESPGHAN Special Interest Group on Gut Microbiota and Modifications suggests it may be considered alongside rehydration therapy, though this remains a conditional recommendation based on very-low-certainty evidence.

The most recent quantitative synthesis specific to this strain and indication, published in 2019, pooled four randomized controlled trials and reported a reduction in diarrhea duration of 0.87 days, with high heterogeneity and very-low certainty of evidence. Since then, additional double-blind trials have been published, including two conducted during and after the COVID-19 pandemic in emergency-department and outpatient settings outside the previously dominant European, mostly inpatient trial base. The updated review therefore aimed to incorporate these newly published trials, re-examine the magnitude and robustness of the effect in the context of changing gastroenteritis epidemiology, and strengthen the previous analysis with a full time-course of diarrhea persistence.

Methodologically, the review followed the PRISMA 2020 statement and the Cochrane Handbook, with the protocol registered in PROSPERO. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2 tool, which evaluates five domains including the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. The search covered MEDLINE via PubMed, Embase, Scopus, and the Science Citation Index Expanded from inception to April 1, 2026, with no language or date restrictions. Random-effects models pooled mean differences and risk ratios, and the certainty of evidence was appraised via the GRADE approach. Because the DerSimonian-Laird estimator may underestimate between-study variance when the number of trials is small, the authors prespecified a sensitivity analysis using the restricted maximum likelihood estimator with the Hartung-Knapp adjustment, which yields more conservative confidence intervals under these conditions.

The six included trials were conducted in Italy, Türkiye, Poland, Paraguay, and Thailand, randomizing children aged between 3 months and 5 years. Three trials were conducted in hospitalized children and three in outpatient or emergency-department settings. Four trials were double-blind and placebo-controlled, and two were single-blind. The daily dose of the strain ranged from 1 x 10^8 to 4 x 10^8 colony-forming units, administered for 5 days in all trials except one lasting 7 days. In all trials, the probiotic was given in addition to rehydration therapy, with placebo as the comparator in four trials and no treatment in two. No trial was judged to be at high risk of bias, though five trials were rated as having some concerns, largely related to blinding of outcome ascertainment or absence of prospective registration.

Beyond the primary outcome, the review examined the proportion of children with persisting diarrhea at successive time points. The treatment effect was modest at 24 hours, with a risk ratio of 0.87, then became substantially greater at 48 hours, with a risk ratio of 0.45, and reached its maximum at 72 hours, with a risk ratio of 0.41, roughly a halving of the risk of persisting diarrhea. The benefit remained statistically significant at 96 and 120 hours, though attenuated as most children in both groups recovered. This temporal pattern suggests that any clinical benefit of the strain is concentrated in the first two to three days of illness. Two trials also showed fewer watery stools per day on days 2 and 3, while the pooled estimate for duration of hospitalization, based on only two trials, was not statistically significant. No serious or treatment-related adverse events were reported across the trials, and where adverse events were recorded, their frequency was comparable between the probiotic and control groups.

A central observation of the review is the concordance between blinding, risk of bias, and effect size. The two single-blind trials produced the largest effects, with a pooled mean difference of 0.99 days, whereas the four double-blind trials yielded approximately half the magnitude, 0.42 days, with markedly lower heterogeneity. The formal test for subgroup differences was not statistically significant, an expected limitation given only six trials, but the pattern is consistent with the well-documented tendency of unblinded trials to inflate subjective outcomes. Because diarrhea duration is a caregiver-ascertained endpoint, trials without participant blinding may be particularly vulnerable to performance and detection bias. The double-blind estimate may therefore provide a more conservative, and possibly less biased, reflection of the true effect. The authors also note that the two post-pandemic trials showed a smaller and more homogeneous effect than the pre-pandemic trials, a finding compatible with the hypothesis that a changing etiological landscape may modify probiotic efficacy, though it cannot be disentangled from differences in design, setting, and dose, and rests on only two trials.

The authors conclude that Limosilactobacillus reuteri DSM 17938 produces a small, probably genuine reduction in the duration of childhood acute gastroenteritis and a moderate reduction in diarrhea persistence at 48 to 72 hours, with a favorable safety profile, but that the effect on the primary outcome is of uncertain clinical importance and rests on very-low-certainty evidence. Future research should prioritize adequately powered, double-blind trials with systematic pathogen characterization, standardized definitions of diarrhea resolution, and intention-to-treat analysis, ideally conducted in the current post-pandemic epidemiological context. The recently proposed Probiotic Human Study Design and Reporting recommendations offer a practical framework for this purpose, emphasizing precise strain identification, transparent reporting of dose and viable count, prospective registration, prespecified standardized outcomes, and intention-to-treat analysis. Only trials of this quality will be able to establish whether the small, sub-one-day benefit suggested by the current evidence represents a reproducible and clinically meaningful effect, and to identify the subgroups in which it is most likely to matter.

Subject of Research: Probiotic strain shortens childhood diarrhea by about 16 hours, but evidence remains shaky

Article Title: Efficacy and safety of Limosilactobacillus reuteri DSM 17938 for the treatment of acute gastroenteritis in children: a systematic review and meta-analysis of randomized controlled trials

Article References: Dinleyici, E. C., Indrio, F., Gutierrez-Castrellon, P., & Rosa, D. (2026). Efficacy and safety of Limosilactobacillus reuteri DSM 17938 for the treatment of acute gastroenteritis in children: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Pediatrics, 14, Article 1941872. https://doi.org/10.3389/fped.2026.1941872

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1941872

Keywords: Limosilactobacillus reuteri DSM 17938, probiotics, acute gastroenteritis, children, diarrhea, meta-analysis, systematic review, pediatrics, GRADE, microbiota, Efficacy, safety