Potential Benefits of Gut Microbiota Modulation in Chronic Obstructive Pulmonary Disease

Background: The gut-lung axis is increasingly recognized. This study aimed to find out whether and how the gut microbiome involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Methods: Gut microbiota was characterized via 16S rRNA gene sequencing in COPD patients and a smoking-induced mouse model. Gut dysbiosis was induced by antibiotic cocktail (ABX) and restored by fecal microbiota transplantation (FMT). Plasma metabolomics was conducted using liquid chromatography-mass spectrometry (LC-MS), and pathway analysis was performed with MetaboAnalyst 5.0. Differentially expressed genes were identified by RNA sequencing and functionally interpreted through gene set enrichment analysis (GSEA). Results: Both COPD patients and mice showed altered gut microbiota, characterized by a unique microbial composition and reduced diversity. ABX induced gut dysbiosis exacerbated pathological lung changes, impaired lung function, and promoted Treg cell exhaustion in COPD mice. Restoration of gut homeostasis via FMT attenuated these alterations. Higher plasma levels of acetylcholine (ACh) were observed in COPD mice, while the highest ACh levels were found in ABX treated COPD mice compared to controls. Notably, ACh levels correlated positively with genus Parasutterella , which was more abundant in COPD mice, and inversely with genera Candidatus Saccharimonas and Lactobacillus , which were predominant in control mice. Metabolomic pathways analysis revealed enrichment in unsaturated fatty acids biosynthesis and purine metabolism in COPD mice relative to controls. Conclusion: These findings highlight the involvement of the gut microbiome in COPD development and suggest that maintaining gut homeostasis may represent a novel therapeutic strategy for COPD. Keywords: COPD, gut, metabolomics, microbiome