To identify the mechanism of inflammatory bowel disease by using human microbe mono-associated mouse

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H02534
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: KANAI TAKANORI 慶應義塾大学, 医学部(信濃町), 教授 (40245478)
• Co-Investigator(Kenkyū-buntansha): 長沼 誠 慶應義塾大学, 医学部, 講師 (00265810) ; 久松 理一 杏林大学, 医学部, 教授 (60255437)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 腸内細菌

Outline of Final Research Achievements

We transplanted feces of ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) patients to germ-free (GF) mice (UC mice or PSC/UC mice). The ratio of Th17 cells was significantly increased in the liver of the PSC/UC mice compared to the UC mice. Klebsiella pneumonia (Kp), Proteus mirabillus, Enterococcus gallineum were frequently detected in feces of PSC+UC patient. We inoculated these three bacteria to GF mice (3 microbe mix mice; 3 mix mice). Th17 cells were accumulated in the liver. We also confirmed 3mix mice induce severe liver damage after DDC treatment compare to UC mice. Kp is found in the lamina propria of Kp mono associated mice. Kp induced epithelial cell apoptosis by using co-culture of Kp and human colon epithelial cells. As above, we revealed Kp destroys intestinal epithelial cells and induces "leaky gut" in the pathological condition of PSC.

Free Research Field

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