The KEGG pathways in the MC group and NC group showed significant differences. In the NC group, the basic metabolic pathways such as amino sugar and nucleotide sugar metabolism (ko00520), O-antigen nucleotide sugar biosynthesis (ko00541), and primary bile acid biosynthesis (ko00120) were significantly upregulated. The pathways enriched in the NC group have clear biological significance.
Amino sugar and nucleotide sugar metabolism serve as the foundation for microbial synthesis of cell wall components (peptidoglycan) and extracellular polysaccharides. Metabolic products of amino acids (such as glutamate and arginine) can participate in the synthesis and activation of immune cells, modulating the host's immune function and reducing systemic inflammatory responses. Nucleotide sugar metabolism is involved in the repair and regeneration of the intestinal mucosa; enhanced function in this pathway can promote the recovery of the intestinal mucosal barrier, reduce endotoxin leakage, and thereby alleviate pulmonary inflammatory responses. These structural components are involved in microbe-host immune interactions, contributing to the maintenance of immune homeostasis.
Primary bile acid biosynthesis is a crucial aspect of host-microbiota co-metabolism. Bile acids, important metabolites synthesized by the liver, are converted into secondary bile acids by gut microbiota. These secondary bile acids not only aid in fat digestion and absorption but also act as signaling molecules, activating nuclear receptors (such as FXR and TGR5) to regulate the host's inflammatory response, metabolic homeostasis, and immune function, playing a vital role in the gut-lung axis. Studies have shown that dysregulation of bile acid metabolism mediated by the gut microbiota can exacerbate pulmonary inflammatory responses in COPD patients through the gut-lung axis. Modulating the gut microbiota can improve bile acid metabolism, reduce airway inflammation, and regulate pulmonary immunity via the gut-lung axis, suggesting that modulating the gut microbiota is a potential therapeutic strategy for improving COPD.
The enrichment of these pathways suggests that the gut microbiota in the NC group may be more active in maintaining basic metabolism and immune regulatory functions.