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Elucidation the mechanism between western diet and carcinogenesis via gut microbiome

Research Project

Project/Area Number 21K08686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKumamoto University

Principal Investigator

Arima Kota  熊本大学, 大学院生命科学研究部(医), 特定研究員 (10792616)

Co-Investigator(Kenkyū-buntansha) 石本 崇胤  熊本大学, 病院, 特任教授 (00594889)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腸内細菌叢 / コリバクチン産生大腸菌 / 大腸癌 / 西洋型食生活 / microbiome / 大腸がん
Outline of Research at the Start

ヒト腸内細菌叢の総重量は肝臓に匹敵し、免疫や代謝など様々な影響を及ぼすことから1つの臓器とも例えられる。ヒト寄生細菌の9割は大腸内に生息しており、直接細菌と接することから悪性腫瘍の中でも大腸癌と強く関連することが示唆されている。また腸内細菌叢は食事やライフスタイルとも密接に関連しており、交絡因子が多数存在することから、詳細な解析には食生活や嗜好品などを含む包括的なデータベースが必要となる。本研究の目的は、大腸癌の危険因子として知られる西洋型食生活が腸内細菌叢を介して大腸癌発癌および進展に与える影響について大規模コホート研究を用いて検証し、そのメカニズムを明らかにすることである。

Outline of Final Research Achievements

We hypothesized that the association of western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+ E. coli.
The association of the western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+ E. coli. Multivariable-adjusted hazard ratios for the highest tertile of the western diet score were 3.45 for pks+ E. coli-high tumors, 1.22 for pks+ E. coli-low tumors, and 1.10 for pks+ E. coli-negative tumors. We have found that the association of western diet with colorectal cancer incidence is stronger for tumors containing higher amounts of pks+ E. coli. Our findings provide evidence supporting the role of the gut microbiota in mediating the pathogenic link between diet and colorectal cancer. This study also underscores the importance of diet as a modifiable factor that may contribute to cancer prevention.

Academic Significance and Societal Importance of the Research Achievements

赤身肉や高脂肪食を中心とした食事である西洋型食生活が特定の細菌・毒素を介して明らかに大腸がんの発癌リスクを高めることが示唆された。医療費および薬剤費が年々膨大となる本邦において、予防医療は今後益々重要になる研究分野の一つである。食生活による大腸癌発癌リスク著増を示す当研究は、国民に対して食生活において警鐘を鳴らす一報となり、また癌研究においては腸内細菌叢と大腸癌発癌におけるメカニズム解明の一助となると思われる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2024 2023 2022 Other

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

  • [Int'l Joint Research] Brigham and Women’s Hospital/Harvard Medical School(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] BWH, Harvard Medical School.(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal carcinoma2024

    • Author(s)
      Takashima Yasutoshi、Kawamura Hidetaka、Okadome Kazuo、Ugai Satoko、Haruki Koichiro、Arima Kota、Mima Kosuke、Akimoto Naohiko、Nowak Jonathan A.、Giannakis Marios、Garrett Wendy S.、Sears Cynthia L.、Song Mingyang、Ugai Tomotaka、Ogino Shuji
    • Journal Title

      Clinical Microbiology and Infection

      Volume: 30 Issue: 5 Pages: 630-636

    • DOI

      10.1016/j.cmi.2024.01.013

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Downregulation of 15-PGDH enhances MASH-HCC development via fatty acid-induced T-cell exhaustion2023

    • Author(s)
      Hu X、Yasuda T、Yasuda-Yosihara N、Yonemura A、Umemoto T、Nakachi Y、Yamashita K、Semba T、Arima K、Uchihara T、Nishimura A、Bu L、Fu Li、Wei F、Zhang J、Tong Y、Wang H、Iwamoto K、Fukuda T、Nakagawa H、Taniguchi K、Miyamoto Y、Baba H、Ishimoto T
    • Journal Title

      JHEP Reports

      Volume: 5 Issue: 12 Pages: 100892-100892

    • DOI

      10.1016/j.jhepr.2023.100892

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Western-Style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses From Two Large Prospective Cohort Studies2022

    • Author(s)
      Arima K, Zhong R, Ugai T, Zhao M, Haruki K, Akimoto N, …Chan AT, Nowak JA, Giannakis M, Ogino S
    • Journal Title

      Gastroenterology

      Volume: 163 Issue: 4 Pages: 862-874

    • DOI

      10.1053/j.gastro.2022.06.054

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 食生活によるコリバクチン産生大腸菌陽性大腸癌発症リスクの検討2022

    • Author(s)
      有馬 浩太、Rong Zhong、鵜飼 知嵩、Jonathan A. Nowak、馬場 秀夫、荻野 周史
    • Organizer
      第122回日本外科学会定期学術集会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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