Strain-Specific Effects of Early-Life Probiotic Supplementation on Respiratory Infections in Infants: A Systematic Review and Meta-Analysis

Background/Objectives: Probiotic and synbiotic supplementation has been proposed as a preventive strategy against respiratory tract infections (RTIs) in early childhood, although evidence in infants and young children remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of probiotic or synbiotic supplementation administered during the first 24 months of life on respiratory infection outcomes. Methods: PubMed/MEDLINE, Embase, and Scopus were systematically searched for randomized controlled trials published between January 2015 and 30 September 2025. Eligible studies included infants and children aged ≤24 months receiving oral probiotics or synbiotics compared with placebo, no intervention, or standard care. The primary outcome was the incidence of at least one upper respiratory tract infection (URTI), while the secondary outcome was the incidence of any RTI. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated according to the GRADE approach. Results: Nine randomized controlled trials were included. Probiotic or synbiotic supplementation did not significantly reduce the risk of URTI (OR 0.95, 95% CI 0.47–1.95; I2 = 78%). A non-significant trend toward a reduced risk of any RTI was observed (OR 0.66, 95% CI 0.35–1.25; I2 = 69%). Exploratory subgroup analyses suggested possible strain-specific effects, with signals observed for Bifidobacterium longum subsp. infantis in relation to URTI prevention and Lactiplantibacillus plantarum ATCC 202195 for reduction in any RTI. However, these findings were based on a limited number of studies and should be interpreted cautiously. No serious adverse events attributable to supplementation were reported. Conclusions: Current evidence does not support the routine use of probiotic or synbiotic supplementation for the prevention of respiratory infections in children aged ≤24 months. However, potential strain-specific benefits warrant further investigation in adequately powered randomized trials.