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Maintenance of Intestinal Homeostasis by Symbiotic Bacteria Residing in Intestinal Immune-inducing Tissues and Its Association with Crohn's Disease

Research Project

Project/Area Number 17K17686
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Immunology
Research InstitutionWaseda University (2018-2020)
Chiba University (2017)

Principal Investigator

Shibata Naoko  早稲田大学, ナノ・ライフ創新研究機構, 次席研究員(研究院講師) (60794542)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腸管免疫 / 腸内細菌 / 樹状細胞 / 粘膜免疫 / 日和見細菌 / 共生細菌
Outline of Final Research Achievements

The present study revealed that while lipopolysaccharide derived from Alcaligenes has low inflammatory activity, it promotes IgA production by B cells and efficiently induces antigen-specific immune responses when used as an adjuvant in vaccines. In addition, when Alcaligenes is overgrown, the form changes from rod-like to filamentous, and cytochrome c accumulated in the bacterial cells with the form change induces apoptosis of dendritic cells. In addition, regarding the effect of Alcaligenes on the onset and aggravation of Crohn's disease, a strong positive correlation was observed between serum Alcaligenes specific IgG antibody and Crohn's disease severity in small intestine colon type Crohn's disease. These results suggest that Alcaligenes specific antibody titer can be a new objective index for Crohn's disease.

Academic Significance and Societal Importance of the Research Achievements

腸管においてIgAは、病原性細菌・ウィルスの侵入阻害や、毒素の中和を行うことが知られており、本研究成果は、Alcaligenes菌が腸管免疫誘導組織であるパイエル板内に共生することで、IgA産生促進を介した生体防御に寄与していることを示唆している。また近年、腸内細菌叢や腸内細菌由来の代謝産物の異常が、関節リウマチの発症や自閉症、神経系の発達や機能に影響することが報告されており、本研究課題から得られる成果は、腸管にとどまらず、将来的には全身性の免疫疾患や炎症性疾患、神経疾患に対する新しい予防法および治療法へと波及する可能性を秘めている。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] 腸内細菌と炎症性腸疾患2020

    • Author(s)
      柴田納央子、清野宏
    • Journal Title

      Pharma Medica

      Volume: 38 Pages: 17-22

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphoid Tissue Resident Alcaligenes Establish an Intracellular Symbiotic Environment by Creating a Unique Energy Shift in Dendritic Cells2020

    • Author(s)
      Hosomi Koji、Shibata Naoko、Shimoyama Atsushi、Uto Tomoya、Nagatake Takahiro、Tojima Yoko、Nishino Tomomi、Takeyama Haruko、Fukase Koichi、Kiyono Hiroshi、Kunisawa Jun
    • Journal Title

      Frontiers in Microbiology

      Volume: 11 Pages: 561005-561005

    • DOI

      10.3389/fmicb.2020.561005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia2019

    • Author(s)
      Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
    • Journal Title

      International Immunology

      Volume: 32 Issue: 2 Pages: 133-141

    • DOI

      10.1093/intimm/dxz071

    • NAID

      120006888456

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Roles for Peyer’s Patch B Cells for Induction of Antigen-specific IgA Antibody Responses in Mice Administered Oral Recombinant Salmonella2019

    • Author(s)
      Hashizume-Takizawa Tomomi、Shibata Naoko、Kurashima Yosuke、Kiyono Hiroshi、Kurita-Ochiai Tomoko、Fujihashi Kohtaro
    • Journal Title

      International Immunology

      Volume: - Issue: 8 Pages: 531-541

    • DOI

      10.1093/intimm/dxz029

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity2018

    • Author(s)
      N. Shibata, J. Kunisawa, K. Hosomi, Y. Fujimoto, K. Mizote, N. Kitayama, A. Shimoyama, H. Mimuro, S. Sato, N. 5 Kishishita, K. J. Ishii, K. Fukase, and H. Kiyono
    • Journal Title

      Mucosal Immunology

      Volume: - Issue: 3 Pages: 693-702

    • DOI

      10.1038/mi.2017.103

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dietary and Microbial Metabolites in the Regulation of Host Immunity2017

    • Author(s)
      Shibata Naoko、Kunisawa Jun、Kiyono Hiroshi
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 2171-2171

    • DOI

      10.3389/fmicb.2017.02171

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 腸内組織内共生細菌由来のシトクロムcによる、宿主樹状細胞のアポトーシス誘導機構2020

    • Author(s)
      柴田納央子、國澤純、安藤正弘、細川正人、堀井俊平、細見晃司、竹山春子、清野宏
    • Organizer
      日本農芸化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Induction of apoptosis in host cells associated with morphological changes of intra-tissue symbiotic bacteria2020

    • Author(s)
      N. Shibata
    • Organizer
      Tokyo 2020 UCSD-IMUST International Joint Research Symposium
    • Related Report
      2019 Research-status Report
  • [Presentation] Morphological changes of intra-tissue opportunistic bacteria, Alcaligenes, are accompanied by cytochrome c accumulation and induce host cell apoptosis2020

    • Author(s)
      N Shibata
    • Organizer
      Rising Stars in Cutting Edge Immunology Research
    • Related Report
      2019 Research-status Report
  • [Presentation] 腸管組織内に共生する日和見細菌アルカリゲネス菌の形態変化に伴う、シトクロムc蓄積と宿主細胞のアポトーシス誘導2019

    • Author(s)
      柴田納央子、國澤純、安藤正弘、細川正人、堀井俊平、細見晃司、竹山春子、清野宏.
    • Organizer
      第71回 日本生物工学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小腸パイエル板組織内共生細 菌アルカリゲネスの免疫機能とアジュバント応用2019

    • Author(s)
      柴田納央子、細見晃司、下山淳史、王韻茹、吉井健、深瀬浩一、清野宏、國澤純
    • Organizer
      日本小児消化管感染症研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity.2018

    • Author(s)
      N. Shibata
    • Organizer
      20th German-Japanese Joint Symposium on Life and Medical Sciences: Interdisciplinary Research for Ageing Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] LPS from lymphoid-tissue resident Alcaligenes induces IgA without excessive inflammation via its weak TLR4 agoinist activity.2018

    • Author(s)
      N Shibata, J Kunisawa, K Hosomi, H Mimuro, S Sato, K J Ishii, H Kiyono.
    • Organizer
      第47回日本免疫学会 学術集会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2022-12-28  

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