Journal Article

The gut-lung axis in COPD: immunomodulatory roles of gut microbiota and novel therapeutic strategies

Chen, Pei-Sheng, Ni, Feng-Xian, Chen, Hui-Hui, Hu, Jie, Xu, Pan, Jiang, Ze-Bo, Huang, Dong-Hui, Wang, Hui-Xian

2026

Overview

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and systemic inflammation, with accumulating evidence implicating gut microbiota dysbiosis as a key modulator of disease pathogenesis via the gut-lung axis. This review synthesizes current knowledge on the bidirectional communication between the gut and lungs, highlighting how microbial metabolites—particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and bile acids—regulate pulmonary immunity through G-protein-coupled receptors, histone deacetylase inhibition, and aryl hydrocarbon receptor signaling. Dysbiosis-driven disruptions in these pathways exacerbate neutrophilic inflammation, impair regulatory T-cell function, and sustain TLR4/NF-κB activation, amplifying lung tissue damage and remodeling. Therapeutic strategies targeting the gut-lung axis show promise in restoring microbial homeostasis and mitigating COPD progression. Probiotics (e.g., Lactobacillus and Bifidobacterium ), prebiotics (e.g., inulin), and dietary interventions (e.g., high-fiber diets) enhance SCFA production, strengthen epithelial barriers, and suppress pro-inflammatory cytokines. Advanced approaches, including fecal microbiota transplantation, nanotechnology-enabled metabolite delivery (e.g., dendrimer-complexed indole-3-acetic acid), and traditional Chinese medicine (TCM) formulations (e.g., the postbiotic formulation Qipian), demonstrate efficacy in preclinical and clinical studies by synchronizing gut-lung microbiota and inhibiting inflammatory pathways. Despite these advances, challenges remain in translating findings to clinical practice, including methodological heterogeneity, antibiotic and corticosteroid confounding, and inter-individual microbiota variability. Future research must integrate multi-omics technologies, validate biomarkers (e.g., Bacteroidales/ Lactobacillus ratio, SCFA levels), and develop personalized interventions to bridge the bench-to-bedside gap. Harnessing the gut-lung axis offers transformative potential for COPD management, shifting the paradigm from symptomatic treatment to disease-modifying strategies rooted in microbiome immunology.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Bacteria / Bile acids / Chronic obstructive pulmonary disease / Dysbacteriosis / Dysbiosis - immunology / Fecal microflora / G protein-coupled receptors / Gastrointestinal Microbiome - immunology / Gut microbiota / gut-lung axis / Histone deacetylase / Homeostasis / Humans / Immunomodulation / Indoleacetic acid / Inflammation / Influence / Intestinal microflora / Lactobacillus / Leukocytes (neutrophilic) / Lung - immunology / Lung - metabolism / Lung - microbiology / Lung diseases / Lungs / Lymphocytes T / Medical treatment / Metabolites / microbial metabolites / Microbiomes / Microbiota / nanoparticles / Nanotechnology / Neutrophils / NF-κB protein / Pathogenesis / Prebiotics / Probiotics / Probiotics - therapeutic use / Pulmonary Disease, Chronic Obstructive - immunology / Pulmonary Disease, Chronic Obstructive - metabolism / Pulmonary Disease, Chronic Obstructive - microbiology / Pulmonary Disease, Chronic Obstructive - therapy / Review / TLR4 protein / Toll-like receptors / Traditional Chinese medicine / Tryptophan