Intestinal microbiota as a therapeutic target of primary sclerosing cholangitis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07931
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kobayashi Yuka 東京大学, 医学部附属病院, 助教 (80724658)
• Co-Investigator(Kenkyū-buntansha): 中川 勇人 東京大学, 医学部附属病院, 助教 (00555609) ; 木下 裕人 公益財団法人朝日生命成人病研究所, その他部局等, 教授(移行) (50645322)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胆管炎 / 炎症性腸疾患 / 小腸 / 腸内細菌叢

Outline of Final Research Achievements

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease causing periductal fibrosis and ductal stenosis. PSC is sometimes accompanied with ulcerative colitis, but the pathogenesis is largely unknown and the treatment is not established. In this study, we examined the role of intestinal microbiota on the pathogenesis of PSC as well as gut-liver axis using PSC and colitis mouse model. Administration of antibiotics to different murine cholangitis model ameliorated the phenotype of cholangitis, such as leukocyte infiltration, fibrosis, and cytokine production. Antibiotic treatment reduced total bacterial number in feces and improved colonic inflammation. These results suggest the critical role of intestinal microbiota on the pathogenesis of PSC and ulcerative colitis.

Free Research Field

消化器病

Academic Significance and Societal Importance of the Research Achievements

原発性硬化性胆管炎は原因不明であり、治療法も確立していない難病である。マウスモデルを用いて胆管炎と腸炎を調節する因子として腸内フローラに着目して検討し、抗生剤による腸内フローラの改変が胆管炎を減弱させることが明らかになった。今後病態に関与する特定の細菌の同定やその制御法を開発することで、原発性硬化性胆管炎の治療が期待できる。