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Elucidation of Inflammatory disorder induced by intestinal dysbiosis

Research Project

Project/Area Number 22K19445
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionKeio University

Principal Investigator

Hase Koji  慶應義塾大学, 薬学部(芝共立), 教授 (20359714)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords腸内細菌 / 粘膜バリア / ディスバイオーシス
Outline of Research at the Start

主要な炎症性腸疾患(クローン病および潰瘍性大腸炎)は、原因不明の希少難治性疾患であり、現時点では完治させる内科的療法は存在しない。炎症性腸疾患患者では腸内細菌の異常が顕著であるが、疾患発症との関わりについては未だ不明な点が多いのが現状である。そこで、本研究ではマウスモデルを用いて、腸内細菌の異常による炎症形成機構について解析を行う。本研究を推進することで、炎症性腸疾患の予防または治療法の開発に貢献する。

Outline of Final Research Achievements

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are rare and intractable diseases of unknown cause. IBD patients show abnormalities in the intestinal microbiota, termed dysibiosis. Therefore, dysbiosis has been considered a factor that exacerbates the disease, but its pathological mechanism has remained unresolved for many years. The applicant has found that mice of the same strain shipped from different breeding facilities show different susceptibilities to colitis. In this study, we focused on differences in the intestinal microbiota due to the growth environment and examined the impact of dysbiosis on colitis susceptibility. As a result, it was found that mice from breeding facilities with high susceptibility to colitis had bacterial species that impair barrier function.

Academic Significance and Societal Importance of the Research Achievements

IBDとディスバイオーシスの相関については数多くの研究が存在するが、その多くは現象論に留まっており、その因果関係や病態メカニズムの解明には至っていない。本研究では、疾患関連菌として未知のバリア分解菌に着目し、その絞り込みに成功しており、ディスバイオーシスによる腸炎悪化のメカニズムの解明に繋がることが期待できる。

Report

(2 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (14 results)

All 2024 2023

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results)

  • [Journal Article] Purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations2024

    • Author(s)
      Hiroaki Shiratori, Kisara M Hattori, Kazuaki Nakata, Takuma Okawa, Seiga Komiyama, Yusuke Kinashi, Yuma Kabumoto, Yuria Kaneko, Motoyoshi Nagai, Tomoko Shindo, Nobuko Moritoki, Yuki I Kawamura, Taeko Dohi, Daisuke Takahashi, Shunsuke Kimura, Koji Hase
    • Journal Title

      International Immunology

      Volume: 36 (5) Issue: 5 Pages: 223240-223240

    • DOI

      10.1093/intimm/dxae003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation.2024

    • Author(s)
      Tang Y, Hase K, Wang JY et al.
    • Journal Title

      Mucosal Immunol.

      Volume: e-publication Issue: 3 Pages: 450-460

    • DOI

      10.1016/j.mucimm.2023.12.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] α-Glucosidase inhibitors boost gut immunity by inducing IgA responses in Peyer’s patches2023

    • Author(s)
      Hattori-Muroi Kisara、Naganawa-Asaoka Hanako、Kabumoto Yuma、Tsukamoto Kei、Fujisaki Yosuke、Fujimura Yumiko、Komiyama Seiga、Kinashi Yusuke、Kato Miki、Sato Shintaro、Takahashi Daisuke、Hase Koji
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1277637-1277637

    • DOI

      10.3389/fimmu.2023.1277637

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles2023

    • Author(s)
      Li Shunyi、Toriumi Hiroki、Takahashi Daisuke、Kamasaki Tomoko、Fujioka Yoichiro、Nagatoishi Satoru、Li Jinting、Liu Yiwei、Hosokawa Takanatsu、Tsumoto Kouhei、Ohba Yusuke、Katayama Yoshiki、Murakami Daisuke、Hase Koji、Mori Takeshi
    • Journal Title

      Biomaterials

      Volume: 303 Pages: 122381-122381

    • DOI

      10.1016/j.biomaterials.2023.122381

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation2023

    • Author(s)
      Shiratori Hiroaki、Oguchi Hiroyuki、Isobe Yosuke、Han Kyu-Ho、Sen Akira、Yakebe Kyosuke、Takahashi Daisuke、Fukushima Michihiro、Arita Makoto、Hase Koji
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 8903-8903

    • DOI

      10.1038/s41598-023-35097-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dietary iodine attenuates allergic rhinitis by inducing ferroptosis in activated B cells.2023

    • Author(s)
      Nakamura Y, Hase K et al.
    • Journal Title

      Sci Rep.

      Volume: 13 Issue: 1 Pages: 5398-5398

    • DOI

      10.1038/s41598-023-32552-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸内代謝物によるストレス性下痢症誘導機構の解明2024

    • Author(s)
      長谷耕二, 石原成美, 木村俊介
    • Organizer
      日本薬学会 第144回年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The pathological link between the intestinal immune system and autoimmune disorders.2024

    • Author(s)
      Koji Hase
    • Organizer
      5th CSI/JSI/KAI Joint Symposium on Immunology“Frontier in Immunology Research in the Aftermath of the Pandemic”
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 病は腸から!知られざる腸内細菌・腸管免疫の功罪.2024

    • Author(s)
      長谷耕二
    • Organizer
      新適塾「未来創薬への誘い」第64回
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The pathological link between the intestinal immune system and autoimmune disorders.2023

    • Author(s)
      Koji Hase
    • Organizer
      The 32nd Hot Spring Harbor International Symposium “Recent Advances in Cell Biology and Immunology”
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸内細菌由来のレチノイン酸~腸管免疫制御における潜在的役割.2023

    • Author(s)
      長谷耕二
    • Organizer
      おかやまバイオアクティブ研究会第63回シンポジウム・日本レチノイド研究会 第34回学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Establishment of oral tolerance requires nutritional signals.2023

    • Author(s)
      Koji Hase
    • Organizer
      The 21st Awaji International Forum on Infection and Immunity.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 栄養シグナルによるリンパ球の腸-_髄連関の制御.2023

    • Author(s)
      長谷耕二
    • Organizer
      第23回Pharmaco-Hematology シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 母体腸内細菌による世代を超えた病態制御.2023

    • Author(s)
      長谷耕二
    • Organizer
      第55回日本動脈硬化学会.
    • Related Report
      2023 Annual Research Report
    • Invited

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Published: 2022-07-05   Modified: 2025-01-30  

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