The effects of Dysbiosis on intestinal stem cells, inflammation, and cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Shimpoh Takayuki 東京大学, 医学部附属病院, 登録研究員 (90791591)
• Co-Investigator(Kenkyū-buntansha): 早河 翼 東京大学, 医学部附属病院, 助教 (60777655)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 炎症性腸疾患 / Dysbiosis / Notch / 消化管幹細胞 / E-cadherin / 樹状細胞

Outline of Final Research Achievements

We tested the positivity of E.coli with pks island sequence, and found that pks+ E.coli is increased in colorectal cancer patients, but decreased in IBD patients, compared to healthy control.
We demonstrated that Tgfbr2-deficient dendritic cells have elevated expression of E-cadherin, and these DCs can directly bind to intestinal epithelial cells and activate Notch signaling, which contribute to the pathogenesis of colitis.
Notch activation in intestinal secretory progenitors lead to dedifferentiation into stem-like cells, and dedifferentiated progenitors can act as a tumor-initiating cells in the mouse intestine.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

E.coli中に含まれるpks island遺伝子の有無を大腸洗浄液中から非侵襲的に検出する方法を確立した。
樹状細胞と上皮の相互作用をIn vitroでモニタリング可能な樹状細胞と上皮オルガノイドの共培養系を構築した。
今回マウスモデルと臨床サンプルで同定した樹状細胞と上皮Notch経路、およびDysbiosisとの関連機構は、ヒトIBDの病態を理解する上で重要な知見であると考えられる。