The Gut-Lung Axis in Respiratory Diseases: Mechanisms, Microbiome Dysbiosis, and Therapeutic Implications. A Comprehensive Review.
TL;DR
It is concluded that the gut-lung axis represents a central, bidirectional framework for understanding respiratory disease pathogenesis, and that future progress will depend on longitudinal, multi-omics, and microbiome-stratified interventional studies to enable precision, microbiome-informed respiratory therapeutics.
Abstract
The gut and lung, though anatomically distinct, are connected through a dynamic, bidirectional communication network known as the gut-lung axis, whereby intestinal microbiota, immune cells, and microbial metabolites regulate pulmonary immunity and homeostasis, while pulmonary perturbations reciprocally alter gut microbial composition and barrier integrity. This narrative review synthesises current evidence on the mechanisms underlying this crosstalk, including immune cell trafficking, short-chain fatty acid and other microbial metabolite signalling, vagal neuroimmune communication, and epigenetic regulation of gut and lung tissues. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library from inception to March 2025, supplemented by manual reference screening, yielding 146 included studies. We examine disease-specific patterns of gut dysbiosis and altered gut-lung signalling across asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, respiratory infections, COVID-19 and post-COVID sequelae, obstructive sleep apnoea, and lung cancer, alongside the reverse pathway by which pulmonary disease and critical illness disrupt intestinal homeostasis. We further review microbiome-targeted therapeutic strategies, including probiotics, prebiotics, dietary interventions, faecal microbiota transplantation, and vagus nerve stimulation, and discuss their current evidentiary limitations. Persistent challenges include predominantly observational study designs, inconsistent methodology, limited multi-omics integration, and a paucity of human mechanistic data. We conclude that the gut-lung axis represents a central, bidirectional framework for understanding respiratory disease pathogenesis, and that future progress will depend on longitudinal, multi-omics, and microbiome-stratified interventional studies to enable precision, microbiome-informed respiratory therapeutics.