분변미생물이식 및 프로바이오틱스 관점에서 마이크로바이옴 기술을 활용한 폐기종의 새로운 치료 전략 모색에 대한 연구

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is manageable, but incurable disease by the standard treatment based on the current practice. As microbiome modulation methods, probiotics administration and fecal microbiota transplantation (FMT) has showed the clinical potentials in various diseases. Therefore, we aimed to investigate the beneficial effect of FMT and specific bacteria administration as probiotics on the emphysema development. Methods: We investigated the clinical characteristics, microbiome, and metabolome in eligible smokers with significant smoking history, defined by more than 30 pack*year smoking history. Sputum and fecal samples were collected for microbiome and metabolome analysis and FMT. The pharmaceutical meta-analytical screening (PMAS) system, which mimicked the intestinal environment, was utilized to screen the candidate bacteria. An emphysema mouse model was used to investigate the effect of FMT and administration of candidate bacteria. Results: Seventy-eight eligible smokers were classified into 19 smokers in non-emphysema, 26 smokers in non-severe emphysema, and 33 smokers in severe emphysema groups. Three groups presented distinct microbiome and metabolome characteristics. In an emphysema mouse model, FMT from non-emphysema and non-severe emphysema group decreased the emphysematous change compared to smoking only group. Administration of HEM20792, which increases the acetic acid and propionic acid levels in the PMAS system, also attenuated emphysematous change compared to smoking only group. Conclusions: FMT from non-emphysema and non-severe emphysema groups and administration of HEM20792 as probiotics attenuated the emphysema development and showed clinical potential as novel treatment strategy for emphysema utilizing gut-lung axis and microbiome technique.