Efficacy of probiotic-supplemented formula in treating chronic diarrhea in children aged 6–43 months: evidence based on a randomized controlled trial

Chronic diarrhea is a common gastrointestinal disorder in young children, leading to nutritional deficiencies, growth retardation, and increased healthcare burdens. Gut microbiota dysbiosis is closely associated with the pathogenesis of chronic diarrhea, but the efficacy of probiotic-supplemented formula tailored to the intestinal microenvironment of Chinese children remains unclear. This study aims to evaluate the therapeutic effect of probiotic-supplemented formula on chronic diarrhea in children aged 6–43 months and explore its potential mechanism through gut microbiota analysis. This randomized, open-label controlled trial was conducted from September 1, 2024, to September 1, 2025, at two hospitals in Shantou City. A total of 160 children aged 6–43 months with chronic diarrhea were enrolled and randomized to the intervention group (n = 80) or control group (n = 80), with 129 participants ultimately included in the efficacy analysis. The intervention group received formula supplemented with Bifidobacterium breve (10 billion CFU/day) as the sole variable, while the control group received the identical formula without Bifidobacterium breve, with both groups consuming the formula for 1 month. The primary outcome was the 1-week cure rate, defined as cure (BSFS = 3,4) or ineffective (BSFS = 5,6,7); efficacy was quantified as the difference in cure rates between the intervention and control groups. Secondary outcomes included time to symptom resolution (diarrhea cessation, stool normalization), changes in fecal microbiota composition, and adverse events. The cure rate in the intervention group was significantly higher than in the control group (37.7% vs. 19.7%, relative risk [RR] = 1.91, 95% confidence interval [CI]:1.08–3.38, P = 0.013). Multivariable logistic regression showed the intervention group had significantly higher odds of efficacy after adjusting for confounders (adjusted odds ratio [OR] = 3.40, 95% CI:1.41–8.22, P = 0.006). Cox proportional hazards modeling indicated a 66% reduction in the risk of persistent diarrhea in the intervention group (hazard ratio [HR] = 0.34, 95% CI:0.21–0.53, P < 0.001). Gut microbiota analysis revealed the intervention group had enriched specific beneficial taxa without the reduction of pre-existing pathobionts. Probiotic-supplemented formula significantly accelerates the resolution of pediatric chronic diarrhea. Mechanistically, this efficacy is driven by specific commensal engraftment rather than mere pathobiont eradication, overcoming the persistent ‘dysbiotic lock’ to improve intestinal clinical outcomes.