Can NASH be induced by leaky gut syndrome ?

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K15029
• Research Institution: Shimane University
• Principal Investigator: 臼田 春樹 島根大学, 学術研究院医学・看護学系, 助教 (30707667)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 腸粘膜バリア / NASH / microbiome

Outline of Annual Research Achievements

昨年度の検討において、NASH誘発食中のトランス脂肪酸が腸粘膜透過性にかかわる可能性が示唆されたため、再検討を行った. しかし再現性のある結果は得られず、どの成分が腸粘膜透過性の亢進にかかわるかは明らかにすることはできなかった. 一方、腸粘膜の透過性亢進は肝機能の指標であるALT、ASTが上昇し始める段階から認められ、その後5か月程度まで継続することが昨年の検討で明らかとなった. そこで、本年は肝臓の障害と腸粘膜の透過性との関連についてさらに検討を行った. NASH誘発食を与えて肝臓の繊維化が認められはじめる給餌3か月後では大腸組織のtightjunctionの発現低下と血中LPSの上昇が認められた. また、DSSによる小腸のダメージの誘発により腸粘膜透過性の増加と肝障害の悪化が認められた. さらに、この障害にはある種の腸内細菌が関与する可能性が示唆された. 以上の結果から、腸粘膜透過性の亢進はNASHの発症や進展を引き起こす可能性が示唆された.

Research Products

• [Journal Article] Efficacy of lubiprostone in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled, phase 2a trial. (2020)
  • Author(s): Kessoku T, Imajo K, Kobayashi T, Ozaki A, Iwaki M, Honda Y, Kato T, Ogawa Y, Tomeno W, Kato S, Higurashi T, Yoneda M, Kirikoshi H, Kubota K, Taguri M, Yamanaka T, Usuda H, Wada K, Saito S, Nakajima A
  • Journal Title: Lancet Gastroenterology & Hepatology Volume: in press Pages: -
  • Peer Reviewed
• [Journal Article] Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial (2020)
  • Author(s): Kamata Y, Kessoku T, Shimizu T, Kobayashi T, Kurihashi T, Sato S, Kuraji S, Aoyama N, Iwasaki T, Takashiba S, Hamada N, Kodama T, Tamura T, Ino S, Higurashi T, Taguri M, Yamanaka T, Yoneda M, Usuda H, Wada K, Nakajima A, Minabe M.
  • Journal Title: Trials Volume: 21 Pages: 291
  • DOI: 10.1186/s13063-020-4201-y.
• [Journal Article] Up-Regulated MicroRNA-27b Promotes Adipocyte Differentiation via Induction of Acyl-CoA Thioesterase 2 Expression. (2019)
  • Author(s): Murata Y, Yamashiro T, Kessoku T, Jahan I, Usuda H, Tanaka T, Okamoto T, Nakajima A, Wada K
  • Journal Title: BioMed research international. Volume: 2019 Pages: 2916243
  • DOI: 10.1155/2019/2916243.
• [Presentation] Effect of cholestyramine on mice model of nonalcoholic steatohepatitis with increased gut permeability. (2019)
  • Author(s): Kessoku T, Kobayashi T, Iwaki M, Ozaki A, Imajo K, Honda Y, Higurashi T, Ogawa Y, Yoneda M, Usuda H, Wada K, Oikawa Y, Tanaka Y, Nakajima S, Saito S, Nakajima A
  • Organizer: Annual Meeting of the Amereican Association for the Study of Liver Diseases
  • Int'l Joint Research
• [Presentation] 腸粘膜バリア機能の破綻を診断しうる新規診断薬の確立 (2019)
  • Author(s): 臼田春樹、新林友美、Kazi Helal Hossain、Israt Jahan、田中 徹也 岡本 貴行、和田 孝一郎
  • Organizer: 第135回日本薬理学会近畿部会
• [Presentation] Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease: The lubiprostone, doubleblind, randomized, placebo-controlled, phase II study (2019)
  • Author(s): Kessoku T, Imajo K, Ogawa Y, Kobayashi T, Honda Y, Kato T, Tomeno W, Kato S, Higurashi T, Yoneda M, Kirikoshi H, Kubota K, Taguri M, Yamanaka T, Usuda H, Wada K, Saito S, Nakajima A
  • Organizer: International liver congress
  • Int'l Joint Research
• [Presentation] Increased levels of bile acid in feces plays an important role in pathophysiology of non-alcoholic steatohepatitis (2019)
  • Author(s): Kessoku T, Kobayashi T, Imajo K, Honda Y, Ogawa Y, Higurashi T, Kato S, Yoneda M, Oikawa Y, Tanaka Y, Nakajima S, Usuda H, Wada K, Saito S, Nakajima A
  • Organizer: International liver congress
• [Remarks] 第3回黒潮カンファレンス
  • URL: https://www.med.shimane-u.ac.jp/gakkai/kuroshio3rd/
• [Remarks] 島根大学医学部薬理学講座
  • URL: https://www.med.shimane-u.ac.jp/pharmacology/index.html