Targeting the gut-lung axis in COPD: from microbial metabolites to fecal microbiota transplantation

Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional syndrome manifested by persistent airway inflammation, oxidative stress, and progressive airflow limitation, with pathology extending far beyond the lung. The gut-lung axis has emerged as a pivotal paradigm for understanding this systemic nature, underscoring the regulatory potency of gut microbiota-derived metabolites in inter-organ immune and metabolic crosstalk. Accumulating evidence suggests that COPD is intricately linked to gut microbiota dysbiosis and widespread disturbances in bioactive metabolites, particularly short-chain fatty acids (SCFAs), tryptophan-related amino acids (AAs), and bile acids (BAs). These metabolic aberrations exacerbate pulmonary inflammation by dysregulating immune homeostasis, compromising intestinal barrier integrity, and skewing redox balance. Fecal microbiota transplantation (FMT), as a strategy capable of comprehensively reconstituting gut microbial and metabolic homeostasis, has demonstrated potential in preclinical and translational settings to attenuate pulmonary injury via the gut-lung axis. This review centers on gut microbiota-associated metabolites, systematically summarizing their roles in COPD pathogenesis and critically evaluating the emerging evidence and mechanistic basis by which FMT recalibrates COPD progression through metabolic pathways, thereby providing a robust theoretical framework for developing precision gut microbiota-targeted systemic therapeutic strategies.