Gut Microbiota-Immune Interactions in Chronic Lung Diseases: An Emerging Cross-Disease Perspective Gut-Lung Axis in Chronic Lung Disease.

Chronic lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary fibrosis, remain major causes of morbidity and mortality despite advances in pharmacological treatment. Emerging evidence suggests that these conditions are influenced by a bidirectional gut-lung axis, through which intestinal microbiota, microbial metabolites, epithelial barrier integrity and mucosal immune programming shape pulmonary inflammation, tissue remodelling and host defence. In this narrative review, we synthesise current clinical and experimental evidence linking gut microbiota-immune interactions to these four chronic lung diseases. Rather than treating dysbiosis as a uniform process, we distinguish shared and disease-specific microbial signatures, including depletion of short-chain fatty acid (SCFA)-producing taxa, delayed microbial maturation, reduced faecal microbial diversity, expansion of pathobionts and altered bile-acid or tryptophan metabolism. We further summarise how SCFAs, tauroursodeoxycholic acid, tryptophan-derived indole metabolites and microbial fragments may regulate Th2 and Th17 inflammation, Th17/Treg balance, neutrophil function, epithelial barrier integrity and fibrotic remodelling. Microbiota-targeted strategies, including dietary fibre and prebiotic approaches, probiotics, synbiotic formulations, faecal microbiota transplantation and selected microbiota-modulating compounds, have shown protective effects in multiple preclinical models, whereas clinical evidence remains limited by small sample sizes, short follow-up, heterogeneous interventions and incomplete mechanistic endpoints. We also discuss unresolved issues, including animal-to-human translation and the difficulty of distinguishing gut-derived from airway-derived microbial signals. A more precise understanding of shared and disease-specific gut-lung circuits may support the rational development of mechanism-informed microbiota-targeted adjunctive strategies for chronic lung disease.