Emphysema severity-associated gut microbiota modulates smoke-induced emphysema: evidence from fecal microbiota transplantation

BACKGROUND: Cigarette smoking is the key risk factor for chronic obstructive pulmonary disease, but even similar levels of smoking can result in different disease severity. We hypothesize that differences in gut microbiota and metabolites contribute to differences in emphysema severity through the gut-lung axis. In this study, we compared the microbiome and metabolome among non-emphysema, non-severe emphysema and severe emphysema groups. Additionally, the impact of fecal microbiota transplantation from non-emphysema, non-severe emphysema and severe emphysema groups on emphysema were investigated. METHODS: A total of 78 participants with a smoking history were included in this study and categorized into three groups: non-emphysema, non-severe emphysema, and severe emphysema. Gut microbiota and metabolites were analyzed, and germ-free mice underwent fecal microbiota transplantation with feces from donors representative of each group prior to smoking exposure. RESULTS: Significant differences in gut microbiota and metabolites were observed among the groups, with lower acetic acid levels in patients with severe emphysema, and a greater abundance of Prevotellaceae and Megasphaera in patients without emphysema. Fecal microbiota transplantation from donors with severe emphysema worsened lung pathology in mice subjected to smoking exposure, whereas fecal microbiota transplantation from donors without emphysema attenuated emphysema development. CONCLUSIONS: Gut microbiota and metabolites in participants with a smoking history differ according to the presence of emphysema and its severity, and can affect emphysema development. This suggests a role for gut microbiota in lung disease and provides a foundation for exploring gut microbiota as a potential therapeutic target for chronic obstructive pulmonary disease.