Gut microbial modulation attenuates emphysema development via suppression of inflammation and apoptosis

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is the treatable, but hardly curable disease associated with significant morbidity. Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. However, the therapeutic implication of the gut microbiome for COPD remains unclear. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. Methods: To modulate the gut microbiome, fecal microbiota transplantation (FMT), diet modification, or both were used in mice exposed to smoking and poly I:C for an emphysema model. We analyzed emphysema severity using mean linear intercept (MLI) and apoptosis using TUNEL assay. Microbiome analyses were also performed in feces and fecal extracellular vesicle. Results: MLI was significantly increased with smoking exposure. FMT or high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN- γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In microbiome analysis, Bacteroidaceae and Lachnospiraceae increased with FMT and HFD. The fecal SCFA concentration was also notably higher with FMT and HFD. Conclusions: FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.