2021 Fiscal Year Final Research Report

Oral dysbiosis increases a risk of hepatic carcinogenesis

Research Project

PDF

Project/Area Number	19K08361
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	University of Tsukuba
Principal Investigator	Mizokami Yuji 筑波大学, 医学医療系, 客員研究員 (70268556)
Co-Investigator(Kenkyū-buntansha)	鈴木英雄筑波大学, 医学医療系, 准教授 (00400672) 蕨栄治筑波大学, 医学医療系, 講師 (70396612) 内田文彦筑波大学, 医学医療系, 講師 (70736008) 岡田浩介筑波大学, 医学医療系, 准教授 (80757526) 正田純一筑波大学, 医学医療系, 教授 (90241827)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	NASH / 歯周病 / Nrf2 / 遺伝子改変マウス / LPS
Outline of Final Research Achievements	We fed WT mice, Nrf2-KO mice and macrophage-specific Nrf2 gene rescue mice which were generated based on Nrf2-KO mice, with a high-fat die coupled with P.g bacteria-derived LPS, and induced NASH. By comparing the phenotype of NASH, we studied the biological role of Nrf2 in periodontal disease bacteria-related NASH in the mice. Transcription factor Nrf2, especially Nrf2 in macrophage, inhibited hepatic inflammation and fibrogenesis, which in turn played a preventive role in the onset of NASH.
Free Research Field	消化器病学
Academic Significance and Societal Importance of the Research Achievements	歯歯周病原菌のリポ多糖を介した腸肝連関という新しい視点から非アルコール性脂肪性肝疾患の進展機序を明らかにしようとした．高脂肪食とP.g 菌由来のLPS投与によるNASHモデルにおいて，Nrf2遺伝子の欠失は，肥満とインスリン抵抗性の改善を介さずに肝組織の炎症と線維化を悪化させた．これらの結果より，歯周病菌関連NASHにおいて，転写因子Nrf2，特にKupffer細胞を含むマクロファージにおけるNrf2は，防御的に機能することが示唆されことは意義が大きい．