Mechanisms by which complex carbohydrates influence immune imbalance in COPD via the gut–lung axis: from colonic fermentation to pulmonary immune responses

Chronic obstructive pulmonary disease (COPD) is characterized not only by local airway inflammation and tissue injury, but also frequently by persistent systemic immune imbalance. After entering the colon, complex carbohydrates can be converted by the gut microbiota into gut-derived molecules such as short-chain fatty acids (SCFAs) and tryptophan metabolites, which may further influence the pulmonary immune status in COPD. These effects are mainly related to the regulation of colonic fermentation kinetics and metabolite production by substrate structure, as well as to the actions of selected metabolites on pulmonary immune cells and airway epithelium after intestinal absorption and systemic distribution. The monosaccharide composition, glycosidic linkage type, degree of branching, and degree of polymerization of complex carbohydrates can affect colonic fermentation kinetics and further alter the production ratio of SCFAs and tryptophan metabolites. SCFAs are the main candidate metabolites linked to the regulation of aberrant neutrophil recruitment, alveolar macrophage inflammatory status, the Treg/Th17 balance, and airway epithelial barrier integrity; selected tryptophan metabolites are mainly involved in mucosal defense and epithelial repair. In COPD, bile acids are more likely to be associated with microaspiration from gastroesophageal reflux and local microecological alterations. Complex carbohydrates may participate in the regulation of immune imbalance in COPD by affecting the production, distribution, and local pulmonary actions of gut-derived metabolites, but the quantitative relationships among these processes across the gut, blood, and lung, as well as their specific pulmonary effects in COPD, still require further clarification, particularly in human studies with synchronized sampling.