New inflammatory disease concept based on the macro-regulatory system

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KT0067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: The University of Tokyo
• Principal Investigator: Hirata Yoshihiro 東京大学, 医科学研究所, 准教授 (10529192)
• Project Period (FY): 2018-07-18 – 2021-03-31
• Keywords: 胆管炎 / 大腸炎 / 腸肝相関 / 神経 / 腸内細菌叢 / サイトカイン

Outline of Final Research Achievements

To understand the etiology of ulcerative colitis and primary sclerosing cholangitis, we have investigated the macro-regulatory system of the gut-liver axis. To stimulate parasympathetic nerve system, acetylcholine analogue was administered to colitis model mouse. Colitis was ameliorated without apparent changes on microbial number or composition, but cholangitis, which was also observed in our colitis model mouse, was not affected by the treatment. In another primary sclerosing cholangitis model mouse, antibiotic treatment effectively reduced the disease activities, such as inflammatory cell infiltration, fibrosis, and epithelial cell abnormality with the reduction of stool bacterial number, suggesting the important role of microbiota on gut-liver axis. IL-33 administration induced the intrahepatic bile duct epithelial hyperplasia with leukocytes infiltration, but showed little effect on the colonic phenotype or microbiota, suggesting limited role of IL33 on gut-liver axis.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

腸管と肝臓など多臓器にまたがる調節機構は十分に解明されていない。本研究ではしばしば合併がみられるものの原因不明である潰瘍性大腸炎と原発性硬化性胆管炎が様々な相互因子、マクロ調節機構で制御されている可能性について検討した。今回の検討で、腸内細菌叢が潰瘍性大腸炎、胆管炎のどちらにも増悪因子として関与しており、肝臓と腸管のマクロ調節機構の一部となっていることが明らかになった。今後腸内細菌叢に影響を与える因子やその制御法を開発することで、これらの病気の原因解明や新規治療法に役立つと考えられる。