• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Dietary factors modulate the intestinal mucosal injury induced by methotrexate.

Research Project

Project/Area Number 18K10985
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionTokyo National Hospital (Clinical research) (2019-2020)
University of Tsukuba (2018)

Principal Investigator

OKA SHOMI  独立行政法人国立病院機構東京病院(臨床研究部), 臨床研究部, 研究員 (60744191)

Co-Investigator(Kenkyū-buntansha) 古川 宏  独立行政法人国立病院機構東京病院(臨床研究部), 臨床研究部, 臨床研究部長 (00372293)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords病因・病態 / メトトレキサート / 腸上皮傷害 / 腸内細菌 / メタボローム / 薬剤誘発性消化管障害 / 腸内細菌叢
Outline of Final Research Achievements

Animal models of methotrexate (MTX)-induced intestinal mucosal injury were developed to represent the gastrointestinal disorder by MTX. We tried to reveal how dietary factors influence the intestinal toxicity of MTX. Microbiome and metabolome analyses on the feces samples suggested the similarity of the intestinal environments of the mice fed with normal chow and high fat high sucrose diet modified in which casein was replaced by soybean derived proteins. High fat high sucrose diet could modify the toxicity of MTX on intestinal epithelia due to the altered MTX distribution by the composite change of the intestinal environments.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢解析とメタボローム解析の結果から、食餌による腸内細菌叢・腸内代謝産物などの腸内環境の変化がメトトレキサートによる消化管傷害増強に関与していることが示唆された。メトトレキサートの消化管傷害を防ぐことが可能な単独の腸内細菌や代謝産物は同定されなかったが、このことは、複合的な腸内細菌群や代謝産物群がメトトレキサートの消化管傷害を防いでいることを示唆している。この研究成果から、メトトレキサートによる消化管傷害の発症には複雑な要因が関わっていると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response.2021

    • Author(s)
      Higuchi T, Oka S, Furukawa H, Tohma S, Yatsuhashi H, Migita K.
    • Journal Title

      Hum Genomics

      Volume: 15 Issue: 1 Pages: 6-6

    • DOI

      10.1186/s40246-020-00301-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case-Control Study2020

    • Author(s)
      Furukawa H, Oka S, Shimada K, Okamoto A, Hashimoto A, Komiya A, Saisho K, Yoshikawa N, Katayama M, Matsui T, Fukui N, Migita K, Tohma S.
    • Journal Title

      Front Med (Lausanne)

      Volume: 17 Pages: 599794-599794

    • DOI

      10.3389/fmed.2020.599794

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of methotrexate-induced intestinal mucosal injury by dietary factors2019

    • Author(s)
      Higuchi T, Yoshimura M1, Oka S1, Tanaka K, Naito T, Yuhara S, Warabi E, Mizuno S, Ono M, Takahashi S, Tohma S, Tsuchiya N, Furukawa H.
    • Journal Title

      Hum Exp Toxicol

      Volume: In press Issue: 4 Pages: 500-513

    • DOI

      10.1177/0960327119896605

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 関節リウマチ関連間質性肺病変に関連する自己抗体2020

    • Author(s)
      岡笑美,古川宏,島田浩太 岡本享,橋本篤,小宮明子,税所幸一郎,吉川教恵,片山雅夫,松井利浩,福井尚志,右田清志 當間重人
    • Organizer
      第74回国立病院総合医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 関節リウマチ関連間質性肺病変に関連する自己抗体2020

    • Author(s)
      岡笑美,古川宏,島田浩太 岡本享,橋本篤,小宮明子,税所幸一郎,吉川教恵,片山雅夫,松井利浩,福井尚志,右田清志,當間重人
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dietary Factors Modulate Gastrointestinal Adverse Effects of Methotrexate.2018

    • Author(s)
      Higuchi T, Yoshimura M, Oka S, Kawasaki A, Warabi E, Mizuno S, Ono M, Takahashi S, Tohma S, Tsuchiya N, Furukawa H.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食餌によるメトトレキサート毒性の増強2018

    • Author(s)
      樋口貴士,吉村美郁,岡笑美,川崎綾,蕨栄治,水野聖哉,小野栄夫,高橋智,當間重人,土屋尚之,古川宏
    • Organizer
      第22回腸内細菌学会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi