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Evidence-Based Supplement Research
Evidence-Based Supplement Research

Study Design

Type
Systematic Review
Population
children (4-18 years) with FAPDs
Methods
Eight databases searched up to October 2025 for RCTs evaluating probiotic interventions; network meta-analysis with random-effects model

Background

Functional abdominal pain disorders (FAPDs) are common pediatric gut-brain interaction disorders that substantially impair quality of life and lack effective pharmacologic or behavioral treatments. Given their biological plausibility, probiotics have emerged as a promising therapy, yet evidence remains inconsistent due to strain-specific effects and heterogeneous study designs.

Methods

Eight databases (PubMed, Embase, Web of Science, CENTRAL, CNKI, VIP, Wanfang, and CBM) were searched up to October 2025 for randomized controlled trials (RCTs) evaluating probiotic interventions in children (4-18 years) with FAPDs. Eligible comparators included placebo, no treatment, or other probiotics. Primary outcomes were global improvement, complete pain resolution, pain severity, and pain frequency. Data were synthesized using a frequentist random-effects network meta-analysis (Stata 17.0, mvmeta command), and treatment efficacy was ranked by SUCRA. Risk of bias was assessed with the Cochrane RoB 2.0 tool, and evidence certainty with CINeMA. Sensitivity and meta-regression analyses evaluated the robustness of findings and the influence of dosage, duration, strain composition, age, and country.

Results

21 RCTs (n = 1,807; published 2003-2023) were included, involving children aged 4-18 years with FAPDs diagnosed mainly by Rome III criteria. Interventions included various probiotic strains (e.g., L. reuteri DSM 17938, L. rhamnosus GG, B. longum DM8504, Bacillus clausii), synbiotics, and prebiotics. In the primary network meta-analysis, probiotics significantly improved all major outcomes versus placebo-global improvement (RR = 1.33, 95% CI 1.03-1.73), complete pain resolution (RR = 1.85, 1.07-3.21), pain severity (MD = -0.72, -1.16 to -0.28), and pain frequency (MD = -1.04, -1.98 to -0.11)-while prebiotics and synbiotics showed no significant benefit. Strain-level analyses identified L. reuteri DSM 17938, L. rhamnosus GG, Bifidobacterium mix, and B. longum (DM8504) as the most effective, with B. clausii consistently ineffective. Sensitivity and meta-regression analyses confirmed result robustness and found no effect modification by dose, duration, strain composition, or demographic factors.

Conclusion

This network meta-analysis shows that probiotics significantly improve symptoms in children with functional abdominal pain disorders. Specific strains-Lactobacillus reuteri DSM 17938, Lactobacillus rhamnosus GG, Bifidobacterium mixtures, and B. longum-demonstrated the most consistent efficacy, supporting a shift toward strain-specific, mechanism-based probiotic therapy in pediatric FAPD.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251218779, identifier CRD420251218779.

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