Systematic review and meta-analysis of randomized controlled trials on pre-, pro-, post- and synbiotic...

The remarkable plasticity of the gut microbiome during the first three years of life offers a critical window of opportunity to influence gut health. The aim of this study is to summarize high quality evidence from randomized controlled trials on the health benefits (respiratory tract infections, diarrheal episodes, febrile days, antibiotic use, microbiome modulation and secretory IgA) of prebiotics, probiotics, synbiotics and postbiotics added to follow-on formula.

A comprehensive literature search for randomized controlled trials (RCTs) using Medline, Embase, Lilacs, and Cochrane was performed up to February 2025 (PROSPERO CRD42024500457). Only RCTs involving healthy children between six months and three years were considered. Quality assessment was done using the ROBINS II tool. Random effects models were used to obtain odd ratio (OR) and number needed to treat (NNT) via meta-analysis.

Out of 2755 search results, 23 studies were included (n = 6984 children) with an overall low risk of bias (14/23) as assessed by the Robins II tool. The OR for respiratory tract infections in pro-,pre- and synbiotics added to a follow-on formula was 0.22 (95 % CI: 0.05-1.09; NNT = 82; CI 95 %: 67-674), 0.84 (95 % CI: 0.66-1.07; NNT = 28; 95 % CI: 11-75) and 0.75 (95 % CI: 0.54-1.05; NNT = 18; 95 % CI: 9-102), respectively. The OR for diarrheal episodes in pre- and synbiotics added to a follow-on formula 1.40 (95 % CI: 0.71-2.79; NNT = 40, 95 % CI: 10-53) and 1.26 (95 % CI: 0.96-1.66; NNT = 17, 95%CI: 8-94), respectively. For the combination of other interventions with other outcomes insufficient studies were available to perform a meta-analysis.

Pre- and synbiotics may help protect against respiratory tract infection, though they do not appear to offer the same benefit for preventing diarrheal episodes. High quality evidence for the effect of biotics added to follow-on formula on health outcomes is sparse. More research is needed to confirm the observed health effects.