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Elucidation of pathological relationship between gut microbiota and peripheral T cell function in human inflammatory diseases

Research Project

Project/Area Number 17K10009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Jun Shimizu  聖マリアンナ医科大学, 医学部, 准教授 (30509964)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腸内細菌叢メタゲノミクス / T細胞機能 / ベーチェット病 / 再発性多発軟骨炎 / 腸内細菌メタゲノミクス / Th17細胞 / 制御性T細胞 / 慢性腎臓病 / アルツハイマー病 / 多発性硬化症 / 免疫学 / T細胞トランスクリプトーム / 自己免疫疾患
Outline of Final Research Achievements

Recent advances in the fields of gut microbiota have revealed the relationships between gut microbe composition/gene function and human health. In this study, we compared the metagenomic data with peripheral T cell function in two rare inflammatory diseases, namely Behcet's disease and relapsing polychondritis. We found that gut microbe numbers decreased and peripheral T cells were overactivated in patients with Behcet's disease. On the contrary, gut microbe numbers increased and peripheral T cells showed reduced responses against stimulation in patients with relapsing polychondritis. We suggest that gut microbe compositional and functional alteration may relate to skewed T cell responses, and subsequent inflammation of the tissues in patients with the two human diseases. We believe that these results propose a new mechanism by which gut microbes affect systemic immune function in several human inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

学術的には、2種のヒト免疫疾患にて腸内細菌叢メタゲノミクスと末梢血T細胞機能を病理的に連結させ、その病態関与の考察を世界で初めて実施したところに意義がある。今後双方において経過観察をする予定であり、診断・治療指針の確立にとって貴重なものにあると推察している。腸内細菌叢メタゲノミクスに関した3論文は、すでに計64論文に引用された(Google scholar調べ)。
社会的には、研究内容を健康管理へと発展させ、市民公開講座や医療講演等で啓蒙を図った。また米国や欧州の再発性多発軟骨炎患者より食事等について医療相談を受ける機会を得て、アドバイスや専門医への紹介等を実施した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (8 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Interaction between SDF1 and CXCR4 Promotes Photoreceptor Differentiation via Upregulation of NFκB Pathway Signaling Activity in Pax6 Gene-Transfected Photoreceptor Precursors.2020

    • Author(s)
      Shimizu J, Suzuki T, Hirotsu C, Ueno H, Takada E, Arimitsu N, Ueda Y, Wakisaka S, Suzuki N.
    • Journal Title

      Ophthalmic Res.

      Volume: 14 Issue: 4 Pages: 1-12

    • DOI

      10.1159/000503929

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet's disease.2019

    • Author(s)
      Shimizu J, Kubota T, Suzuki N et al.
    • Journal Title

      Clinical Rheumatology

      Volume: 9 Issue: 5 Pages: 1-9

    • DOI

      10.1007/s10067-018-04419-8

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of intestinal dysbiosis and T cell dysfunctions in patients with collagen related diseases, such as Behcet's disease and relapsing polychondritis.2019

    • Author(s)
      Shimizu J, Suzuki N.
    • Journal Title

      International Journal of Clinical. Rheumatology.

      Volume: 14 Pages: 130-133

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis.2018

    • Author(s)
      Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Murayama MA, Ueda Y, Wakisaka S, Suzuki T, Suzuki N
    • Journal Title

      PLoS One

      Volume: 20 Issue: 9 Pages: e0203657-e0203657

    • DOI

      10.1371/journal.pone.0203657

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relapsing polychondritis patients were divided into three subgroups: patients with respiratory involvement (R subgroup), patients with auricular involvement (A subgroup), and overlapping patients with both involvements (O subgroup), and each group had distinctive clinical characteristics.2018

    • Author(s)
      Shimizu J, Yamano Y, Kawahata K, Suzuki N.
    • Journal Title

      Medicine (Baltimore).

      Volume: 97 Issue: 42 Pages: e12837-e12837

    • DOI

      10.1097/md.0000000000012837

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organ involvement pattern suggests subgroups within relapsing polychondritis2018

    • Author(s)
      Shimizu J, Yamano Y, Yudoh K, Suzuki N.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 70 Issue: 1 Pages: 148-149

    • DOI

      10.1002/art.40330

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal cell sheets of cortical motor neuron phenotype derived from human iPS cells.2017

    • Author(s)
      Suzuki N, Arimitsu N, Shimizu J, Takai K, Hirotsu C, Ueda Y, Wakisaka S, Fujiwara N, Suzuki T.
    • Journal Title

      Cell Transplant.

      Volume: 26 Issue: 8 Pages: 1355-1364

    • DOI

      10.1177/0963689717720280

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒト末梢血T細胞分化関連遺伝子発現と腸内細菌叢の病理的関連検討2017

    • Author(s)
      清水 潤、鈴木 登
    • Journal Title

      Medical Science Digect

      Volume: 43 Pages: 653-656

    • Related Report
      2017 Research-status Report
  • [Presentation] A third of relapsing polychondritis patients with ear involvement at presentation had airway involvement at the last follow-up with a high mortality rate.2019

    • Author(s)
      Shimizu J, Kawahata K, Yamano Y, Suzuki N.
    • Organizer
      ACR/ARHP annual meeting. 2019.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 再発性多発軟骨炎は気道軟骨炎および耳介軟骨炎の有無により2群に分類される.2019

    • Author(s)
      清水潤、山野嘉久、川畑仁人、鈴木登.
    • Organizer
      第116回日本内科学会総会・講演会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 再発性多発軟骨炎における気道軟骨炎・耳介軟骨炎の有無による群間検討の重要性.2019

    • Author(s)
      清水潤、山野嘉久、川畑仁人、鈴木登.
    • Organizer
      第63回日本リウマチ学会総会・学術集会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] Japanese relapsing polychondritis patients with airway involvement were mutually exclusive with those with ear involvement in the clinical characteristics2018

    • Author(s)
      Jun Shimizu, Noboru Suzuki.
    • Organizer
      米国リウマチ学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulatory T cells with skewed responses and propionate-producing gut bacteria increased simultaneously in patients with relapsing polychondritis2018

    • Author(s)
      Jun Shimizu, Takao Kubota, Noboru Suzuki.
    • Organizer
      米国リウマチ学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 再発性多発軟骨炎で認められた特徴的な腸内細菌叢と免疫異常-健常人およびベーチェット病と比較して2018

    • Author(s)
      清水 潤、久保田孝雄、鈴木 登
    • Organizer
      日本リウマチ学会
    • Related Report
      2018 Research-status Report
  • [Presentation] An abundance of butyrate-producing bacterium in the intestine and increased Foxp3 gene expression of T cells in patients with relapsing polychondritis2017

    • Author(s)
      Shimizu J, Kubota T, Suzuki N
    • Organizer
      米国リウマチ学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ベーチェット病で認められた腸内細菌叢のDysbiosis2017

    • Author(s)
      清水 潤、久保田孝雄、鈴木 登
    • Organizer
      日本内科学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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