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Oral derived bacteria influence intestinal immune system

Research Project

Project/Area Number 16K15293
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKeio University

Principal Investigator

Atarashi Koji  慶應義塾大学, 医学部(信濃町), 准教授 (60546787)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords腸内細菌 / Th1細胞 / クレブシエラ菌 / TH1細胞 / 口腔細菌 / クレブシエラ / Th1 / dysbiosis / 口腔内細菌 / 粘膜免疫
Outline of Final Research Achievements

Intestinal colonization by bacteria of oral origin has been correlated with several gastrointestinal diseases, including inflammatory bowel diseases (IBD). However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. I inoculated saliva samples from IBD patients into germ-free (GF) mice by oral gavage. I have clarified that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize the gut. Although these Klebsiella strains could not colonize the gut of SPF mice with normal microbiota, they preferentially colonize those of SPF mice with dysbiotic microbiota, such as antibiotics treatment. These Klebsiella strains elicit a severe gut inflammation in the context of a genetically susceptible host, such as Il10 deficient mice.

Academic Significance and Societal Importance of the Research Achievements

本研究では、クローン病や潰瘍性大腸炎などの慢性炎症性腸疾患の発症に口腔由来のクレブシエラ属細菌が関与している可能性があることを明らかにした。これまでクレブシエラ菌が炎症性腸疾患に関与していることを示唆するデータは存在したが、直接の関与を証明した初めての結果であり、したがってクレブシエラ属細菌が慢性炎症性腸疾患に対する新たな創薬標的となり得ることが想定されます。そこで、クレブシエラ属細菌を選択的に排除・殺菌する抗生物質などの開発やクレブシエラ属細菌が腸管内に定着させないような薬剤の開発を通して、これら疾患の予防法や治療薬の開発につながることが期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis.2019

    • Author(s)
      Nakamoto N, Sasaki N, Aoki R, Miyamoto K, Suda W, Teratani T, Suzuki T, Koda Y, Chu PS, Taniki N, Yamaguchi A, Kanamori M, Kamada N, Hattori M, Ashida H, Sakamoto M, Atarashi K, Narushima S, Yoshimura A, Honda K, Sato T, Kanai T.
    • Journal Title

      Nat Microbiol.

      Volume: 4 Issue: 3 Pages: 492-503

    • DOI

      10.1038/s41564-018-0333-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation" Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammationx2017

    • Author(s)
      Atarashi K, Suda W, Luo C, Kawaguchi T, Motoo I, Narushima S, Kiguchi Y, Yasuma K, Watanabe E, Tanoue T, Thaiss CA, Sato M, Toyooka K, Said HS, Yamagami H, Rice SA, Gevers D, Johnson RC, Segre JA, Chen K, Kolls JK, Elinav E, Morita H, Xavier RJ, Hattori M, Honda K.
    • Journal Title

      Science

      Volume: 358 Issue: 6361 Pages: 359-365

    • DOI

      10.1126/science.aan4526

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 口腔由来クレブシエラ菌の腸内定着と炎症誘導2018

    • Author(s)
      新幸二
    • Organizer
      第 27 回東京免疫フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ヒト腸内フローラと免疫機能2017

    • Author(s)
      新幸二
    • Organizer
      平成29年度 (公社)日本実験動物学会 維持会員懇談会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 口腔細菌による腸管免疫系活性化機構の解明2016

    • Author(s)
      新幸二
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 口腔内細菌による腸管免疫活性化機構の解明2016

    • Author(s)
      新幸二
    • Organizer
      フォーラム2016 衛生薬学・環境トキシコロジー
    • Place of Presentation
      昭和大学旗の台キャンパス(東京都品川区)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] Th1細胞を誘導する細菌2017

    • Inventor(s)
      本田 賢也、新 幸二、成島 聖子、須田 亙、服部 正平
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Th1細胞を誘導するヒト口腔内細菌2017

    • Inventor(s)
      本田賢也、新幸二、成島聖子、須田亙、服部正平
    • Industrial Property Rights Holder
      本田賢也、新幸二、成島聖子、須田亙、服部正平
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2020-03-30  

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