Early-Life Gut Microbiota and the Pediatric Gut-Lung Axis: A Systematic Review of Clinical, Preclinical, and Mechanistic Evidence

Background/Objectives: The early-life gut microbiota plays a pivotal role in immune maturation and may influence respiratory health through the gut-lung axis. However, evidence linking microbial development, dysbiosis, microbial metabolites, and microbiota-targeted interventions to pediatric respiratory outcomes remains heterogeneous. This systematic review aimed to synthesize clinical and preclinical evidence on the pediatric gut-lung axis and its underlying mechanisms.

Methods

This systematic review followed PRISMA 2020 guidelines and a prospectively registered PROSPERO protocol (CRD420251062905). PubMed, Scopus, and Web of Science were searched for studies published from January 2014 to March 2025. Eligible primary studies included randomized controlled trials, observational studies, and mechanistically relevant animal models. Risk of bias was assessed using RoB 2, the Newcastle-Ottawa Scale, and SYRCLE's tool, respectively. Reviews were examined separately to provide mechanistic and translational context without contributing to the primary evidence synthesis.