Comparative efficacy and safety of probiotic for respiratory tract infections in children: a network meta-analysis.

OBJECTIVE: This study aimed to evaluate the comparative efficacy and safety of various probiotic regimens for treating Respiratory tract infections (RTIs) in otherwise healthy children. METHODS: Six Chinese and English databases were searched for randomized controlled trials of probiotics for the RTIs in children published from inception to November 15th, 2025. Pairwise meta-analysis and network meta-analysis were used to assess the efficacy and safety. RESULTS: Eight RCTs enrolling 1,158 children aged 0.69 to 6.4 years from Ukraine, China, Malaysia, India, and Italy were included. Bifidobacterium significantly shortened duration of cough, Lactobacillus reduced duration of illness, Lactobacillus+Bifidobacterium reduced both duration of cough and antibiotic use, and the four-strain combination (Lactobacillus+Bifidobacterium+Enterococcus+Bacillus) reduced durations of fever and cough. Low-certainty evidence suggested superior efficacy of the Lactobacillus+Bifidobacterium over both Bifidobacterium and the four-strain combination for reducing duration of cough, and over Lactobacillus for shortening antibiotic use. Stratified analyses revealed strain-specific effects across RTI subtypes: Bifidobacterium shortened cough in LRTI [-1.12 days, (-1.82, -0.42)]; Lactobacillus reduced illness duration in both URTI [-1.31 days, (-2.19, -0.43)] and LRTI [-1.36 days, (-2.29, -0.43)], and shortened antibiotic use in URTI [-1.70 days, (-2.40, -1.00)]; Lactobacillus+Bifidobacterium shortened fever in URTI [-2.00 days, (-2.57, -1.43)], cough in LRTI [-1.25 days, (-1.84, -0.66)], and both fever -7.10 days, (-8.54, -5.66)] and antibiotic use [-10.50 days, (-13.22, -7.78)] in RRTI; the four-strain combination reduced fever [-1.54 days, (-2.40, -0.68)] and cough [-2.51 days, (-3.89, -1.13)] in RRTI. One RCT reported comparable incidence of gastrointestinal adverse events between probiotic and control groups. CONCLUSION: Moderate- to high-certainty evidence supports Bifidobacterium for reducing cough duration and Lactobacillus for shortening illness duration in children with RTIs. While Lactobacillus+Bifidobacterium demonstrated large-magnitude reductions in cough duration and antibiotic use, these findings derive from low- to moderate-certainty evidence and require verification through rigorously designed randomized clinical trials. Strain-specific effects varied across RTI subtypes, suggesting the need for tailored probiotic selection. Future research should prioritize validating multi-strain efficacy, establish optimal dosing protocols, and evaluate long-term safety profiles to enable evidence-based guideline development. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251074234, identifier CRD420251074234.