Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis

Abstract

Lung disease: Fecal transplants and fiber reduce airway inflammation Fecal transplants and high-fiber diets help to mitigate the lung damage caused by smoking in mice, a finding that could lead to new therapeutic interventions for people suffering from emphysema. A team led by Sei Won Lee and Yong Shin from the University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea, exposed mice to cigarette smoke and a molecule stimulating the immune system to induce chronic lung disease. The researchers then treated the mice with feces from healthy donor animals or fed them a high-fiber diet. Both interventions altered the microbial community in the gut, leading to increased ability to convert dietary fiber into short chaing fatty acid with immune-modulating effects. Consequently, the mice exhibited less inflammation throughout their bodies, including in the lungs, where alveolar structure was protected from destruction.

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-gamma 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,BacteroidaceaeandLachnospiraceae, 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.