The role of the gut–lung axis in persistent inflammation and disease progression in chronic obstructive pulmonary disease: mechanistic evidence and therapeutic implications

Abstract

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease worldwide, and the mechanisms underlying its persistent airway inflammation, systemic inflammation, and acute exacerbations remain incompletely understood. In recent years, the concept of the gut-lung axis has provided a new perspective for understanding the pathophysiological processes of COPD, suggesting that gut microbiota imbalance may participate in the regulation of pulmonary inflammation via this bidirectional pathway. This article systematically reviews the biological basis of the gut-lung axis, focusing on the mechanisms by which the gut microbiota influences pulmonary immune homeostasis through metabolic signals such as short-chain fatty acids, tryptophan derivatives, and bile acids, as well as through intestinal barrier maintenance, immune cell regulation, and microbe-associated inflammatory pathways. Current research indicates that COPD patients exhibit decreased gut microbiota diversity, reduced abundance of short-chain fatty acid-producing bacteria, and increased opportunistic pathogens, alterations correlated with decreased lung function, systemic inflammation, and the risk of acute exacerbations. This article further explores the potential mechanisms by which microbiota imbalance contributes to the persistence of pulmonary inflammation through processes such as disrupted microbial metabolic profiles, intestinal barrier damage, immune cell imbalance, and inflammasome activation, and evaluates potential intervention strategies targeting the gut-lung axis, including probiotics, dietary interventions, traditional Chinese medicine (TCM), and fecal microbiota transplantation (FMT). Overall, based on existing evidence, gut microbiota imbalance may participate in the persistence of chronic inflammation, acute exacerbations, and disease progression in COPD through the gut-lung axis, offering new insights for adjuvant therapy and individualized interventions in COPD. However, current evidence is still primarily derived from observational studies and preclinical research, and future research utilizing prospective cohorts, multi-omics integrative analyses, and randomized controlled trials is required to further validate its causal relationships, intervention effects, and clinical safety.