The gut-lung axis in early life: microbiome-associated mechanisms and clinical relevance

The early-life microbiome is increasingly recognised as a contributor to immune maturation and respiratory health. Early-life microbial colonisation is highly dynamic and shaped by multiple factors. Recently, the gut-lung axis has emerged as a framework describing bidirectional communication between the intestinal microbiota and the respiratory system via microbial metabolites, immune mediators and neuroimmune pathways. Although current evidence is largely derived from studies of bacterial communities, emerging data suggest that other microbial components, including fungi and viruses, may also contribute to gut-lung interactions. This review synthesises current mechanistic and clinical evidence on the gut-lung axis with a specific focus on neonatology. We discuss how early microbiome composition may influence immune regulation, lung development and inflammatory response. Associations between intestinal microbiota alterations and major neonatal morbidities, including bronchopulmonary dysplasia, are discussed, as well as emerging evidence linking early-life microbial imbalance to long-term respiratory outcomes such as recurrent infections and asthma. We further examine emerging translational opportunities, including microbiome- and metabolome-based biomarkers for early risk stratification, and microbiota-targeted interventions. Attention is given to the strengths and limitations of the current evidence base, including the predominance of observational human studies and preclinical animal models. Overall, available evidence suggests that the developing microbiome represents a potentially important mediator of gut-lung communication in early life. However, substantial gaps remain regarding causality, underlying mechanisms and clinical applicability. Further longitudinal and interventional studies are needed to define the role of microbiome-targeted strategies in improving neonatal and long-term respiratory outcomes.