Abstract
Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a 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 the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. 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.
Highlights
Chronic obstructive pulmonary disease (COPD) is a chronic progressive disease with significant worldwide morbidity and mortality[1,2]
We observed that postbiotic short-chain fatty acids (SCFAs) administration attenuated emphysema development, but SCFAs were less effective than a prebiotic high-fiber diet. These results indicate that a prebiotic high-fiber diet has more potent preventive effects, and is associated with better lung function related to emphysema development
Here, we demonstrated the therapeutic potential of fecal microbiota transplantation (FMT) and a high-fiber diet in emphysema treatment
Summary
Chronic obstructive pulmonary disease (COPD) is a chronic progressive disease with significant worldwide morbidity and mortality[1,2]. The overall therapeutic strategy has not changed in recent decades; smoking cessation and bronchodilators are still the main treatment. Pulmonary and systematic inflammation persists in patients with established COPD even after smoking cessation[3]. The maintenance of immune homeostasis may be a critical contributor to the susceptibility of a smoker, and this could be due to interactions between the host immune system and microbes[6,7]. The intimate interactions between gut microbes and the lung were called the gut–lung axis, and microbial dysbiosis in this axis is related to chronic respiratory diseases[8,9,10], relatively well described in allergic airway diseases[11,12]. Modulation of gut microbial dysbiosis using diet (prebiotics) and microbe metabolites (postbiotics) demonstrated a beneficial role in Official journal of the Korean Society for Biochemistry and Molecular Biology
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