Dietary factors modulate the intestinal mucosal injury induced by methotrexate.
Project/Area Number |
18K10985
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Tokyo 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.
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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。
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Report
(4 results)
Research Products
(7 results)
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[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.
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Journal Title
Front Med (Lausanne)
Volume: 17
Pages: 599794-599794
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Hum Exp Toxicol
Volume: In press
Issue: 4
Pages: 500-513
DOI
Related Report
Peer Reviewed
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[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
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[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
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[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
Int'l Joint Research
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[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