The respiratory and gastrointestinal mucosal microbiota serve as the biological foundation for the bidirectional interaction of the “lung-gut” axis. The gut microbiota can influence the development and progression of COPD by modulating immune function. Specific bacterial populations, such as segmented filamentous bacteria (SFB), can directly adhere to intestinal epithelial cells, activating both innate and adaptive immune cells, inducing immune cell differentiation, promoting lymphoid tissue development, and IgA production, thereby maintaining host barrier protection and self-immune balance [53]. Probiotics such as bifidobacteria and lactobacilli can inhibit the colonization of harmful bacteria through the formation of a biological barrier, production of antimicrobial substances, enhancement of antibody levels, and activation of macrophages. The gut mucosal immune system is interconnected with the respiratory mucosal immune system via the common mucosal immune system. When immune function is weakened, opportunistic pathogens can more easily infect and cause pulmonary inflammation or exacerbate existing conditions [47]. Additionally, microbial metabolites (such as short-chain fatty acids, SCFAs, and lipopolysaccharides, LPS) are key mediators in the crosstalk between the lung and gut. LPS, in particular, can enter the bloodstream following gut barrier damage and induce inflammatory responses by activating TLR4 receptors on immune cells [54,55].