대장염의 발생에 장내 미생물 유래 세포밖 소포체가 미치는 역할에 대한 연구

Abstract

The inflammatory bowel disease (IBD) is a group of inflammatory conditions of the intestines. It is divided into ulcerative colitis (UC) and Crohn’s disease (CD) largely. There are many studies the causes on IBD by the interaction between host and commensal bacteria. Stool is composed of 3 major components which are water, indigested foods and commensal bacteria.Dextran sulfate sodium (DSS)-induced colitis is a well-established animal colitis model. Its cytokine profile is similar to the UC conditions unlike CD. The precise mechanism of DSS-induced colitis is not yet elucidated in detail. But there are evidences that DSS is likely to make the mucosal layer weak and eventually leads to the instillation of bacteria into the epithelial tissues. Infiltrated bacteria then induce the inflammation. These bacteria secrete the various functional membrane vesicles to respond to the surrounding milieus.We administered 3% DSS in drinking water for 5 day to C57BL/6 female mice and collect their stool every day. We extracted the extracellular vesicles (EVs) from the stools of DSS colitis and control mice daily. Isolated stool-derived EVs differed from the control EV in yields per stool in one gram and protein pattern in SDS-PAGE. Especially, EV-derived 16S rDNA changed largely compared to the bacteria-derived 16S rDNA. We chose a specific species to extract their EV in the decreased species. The specific species-derived EVs worked as the therapeutic agent in 2% DSS colitis in vivo model.There are no studies regarding stool-derived EVs. Our data imply that stool-derived EVs represent the gut microenvironments. Furthermore, information about some bacteria secreted EVs, chosen by quantitative changes from stool-derived EVs supports that EVs could play a direct role in ameliorating or exaggerating agent on colitis. This information offers new clues about the development of IBD.