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Elucidation of the mechanism of colorectal cancer development by intestinal bacteria with epithelial cytotoxicity

Research Project

Project/Area Number 21K15008
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionYamaguchi University (2022)
Osaka University (2021)

Principal Investigator

Tsuji Shunya  山口大学, 大学院医学系研究科, 助教 (80898370)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsSARS-CoV-2 / 細胞老化 / SASP / 腸内細菌 / 腸内細菌叢 / COVID-19 / 大腸がん / 腸管バリア機構 / Long-COVID
Outline of Research at the Start

大腸がんは、日本において罹患者数1位、死亡者数2位のがんであり、病態解明や新たな治療法の開発が求められている疾患である。近年、大腸がんの発生には、腸内細菌叢の変化が深く関与していることが明らかになってきたが、その発がん誘導機構は不明な点が多い。申請者は、これまでの研究から、早期大腸がん患者で増加している細菌のうち5種が、ヒト正常上皮細胞に細胞傷害性を有し、大腸がん発生初期に生じる腸管バリア機構の破綻に関与する可能性を見出した。そこで、本研究では、これらの細菌が有する上皮細胞傷害機構の解明を通し、大腸がんの予防法や治療法開発への応用を目指す。

Outline of Final Research Achievements

In this study, we started with the aim of clarifying the relationship between the disturbance of the gut microbiota in the SARS-CoV-2 (severe acute respiratory coronavirus 2) infection and the development of colon cancer. As a result, we did not detect any disturbance in gut microbiota after SARS-CoV-2 infection. However, during the course of this research, a phenomenon called cellular senescence was induced in the lungs, which are the main organs infected by the SARS-CoV-2, and became one of the causes of the inflammatory response that persisted even after the virus was eliminated from the body. It was made clear that such a phenomenon may be part of the pathological condition of sequelae that continues even after recovery from COVID-19, called Long COVID, which is currently a global problem.

Academic Significance and Societal Importance of the Research Achievements

新型コロナウイルス感染症(COVID-19)は2019年12月に発生した新興感染症であり、回復した人の10%程度で後遺症が残り、1年以上もその症状が持続してしまうことが問題となっているが、依然としてその原因は明らかになっていない。本研究ではSARS-CoV-2感染により誘導される老化細胞がその原因となっている可能性を明らかにすることができた点で大きな社会的な意義があると考えている。

Report

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

    (3 results)

All 2022 Other

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

  • [Journal Article] SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response2022

    • Author(s)
      Tsuji Shunya、Minami Shohei、Hashimoto Rina、Konishi Yusuke、Suzuki Tatsuya、Kondo Tamae、Sasai Miwa、Torii Shiho、Ono Chikako、Shichinohe Shintaro、Sato Shintaro、et al.
    • Journal Title

      Nature Aging

      Volume: 2 Issue: 2 Pages: 115-124

    • DOI

      10.1038/s43587-022-00170-7

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence- associated inflammatory response2022

    • Author(s)
      Shunya Tsuji, Shohie Minami, Rina Hashimoto, Tatsuya Suzuki, Miwa Sasai, Shiho Torii, Chikako Ono, Shintaro Shichinohe, Shintaro Sato, Masahiro Yamamoto, Tokiko Watanabe, Yoshiharu Matsuura, Kazuo Takayama, Takeshi Kobayashi, Toru Okamoto, Eiji Hara
    • Organizer
      第20回あわじ感染と免疫国際フォーラム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 新型コロナウイルスの感染は細胞老化を引き起こすことで炎症反応が持続することを発見

    • URL

      http://www.biken.osaka-u.ac.jp/achievement/research/2022/167

    • Related Report
      2022 Annual Research Report 2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2024-01-30  

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