The role and mechanism of gut-lung axis mediated bidirectional communication in the occurrence and development of chronic obstructive pulmonary disease

Abstract

The current studies have shown that the occurrence and development of chronic obstructive pulmonary disease (COPD) are closely related to the changes in gut health and its microenvironment, and even some gut diseases have significant clinical correlation with COPD. The dysbiosis of gut microbiota observed in COPD patients also suggests a potential bidirectional interaction between the gut and lung. Communication between the gut and lung may occur through circulating inflammatory cells, gut microbial metabolites, and circulating inflammatory mediators, but the mechanism of bidirectional communication between the gut and lung in COPD is still under study. Therefore, more research is still needed in this area. In this review, we summarize recent clinical studies and animal models on the role of the gut-lung axis in the occurrence and development of COPD and its mechanisms, so as to provide ideas for further research in this field. In addition, we also summarized the negative effects of COPD medication on gut microbiota and the gut microbiota risk factors for COPD and proposed the potential prevention and treatment strategies.

Keywords: Gut microbiota; chronic obstructive pulmonary disease; gut-lung axis.

Figure 1.

Bidirectional communication between gut and lung mediated by gut-lung axis. The bidirectional interaction between the gut and lungs is mainly achieved through immune responses, microbial composition, and metabolites of the gut microbiota. Dendritic cells receive antigens to activate T-lymphocytes and B-lymphocytes mediated immune responses. LPS, as an important component of gram-negative bacteria in gut microbiota, can regulate lung immune homeostasis through the circulatory system. Gut microbiota metabolites, such as SCFAs, promote bidirectional communication between the gut and lungs through blood circulation. DCs, dendritic cells; LPS, lipopolysaccharide; SCFAs, short-chain fatty acids; sIgA, secretory immunoglobulin A.

Figure 2.

Changes of gut microbiota composition in COPD. Changes in gut microbiota were observed in both animal models and clinical studies. Clinically, the dominant bacteria in the gut microbiota of COPD patients at different stages of development were different. COPD, chronic obstructive pulmonary disease; COPD I, COPD severity stages I; COPD I-II, COPD severity stages I and II; COPD II-III, COPD severity stages II and III; COPD III-IV, COPD severity stages III and IV.

Figure 3.

Potential mechanisms of gut microbiota in the pathogenesis of COPD. the disorder of gut microbiota in COPD patients can lead to increased gut permeability, increase the risk of gut bacterial translocation and LPS transfer, and thus promote lung inflammation. The decrease in the abundance of Bacteroides and bifidobacterium can affect the host immune homeostasis by inhibiting the production of sIgA and antimicrobial peptides. Bacteroidetes derived PSA can also prevent airway inflammation by regulating the activity of T lymphocytes to produce IL-10. LPS, Lipopolysaccharide; sIgA, secreted immunoglobulin A; PSA, polysaccharide A.

Figure 4.

Effects and mechanisms of gut microbiota metabolites on lung health. the content of SCFAs in feces of COPD patients is decreased. ① SCFAs can inhibit the phosphorylation of STAT1 by inhibiting the binding of STAT1 and HDAC3, and promote the transformation of pulmonary macrophages into the anti-inflammatory M2 phenotype; ② SCFAs can alleviate lung inflammation by inhibiting the recruitment and activation of mast cells and eosinophils mediated by Th9 cells; ③ SCFAs can inhibit the transition of ILC2 to inflammatory ILC2, thereby alleviating lung inflammation. The increased plasma TMAO levels in COPD patients are associated with all-cause mortality. TMAO stimulates bone-marrow-derived macrophages to secrete chemokines and inflammatory factors, leading to excessive proliferation and migration of pulmonary vascular smooth muscle cells, which is a potential mechanism of pulmonary vascular remodeling. STAT1, signal transducer and activator of transcription 1; HDAC3, histone deacetylase 3; ILC2, group 2 innate lymphoid cells; TMAO, trimethylamine N-oxide.