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Regulation of intestinal environment via Paneth cell function in Kampo herbs

Research Project

Project/Area Number 20K15463
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 38050:Food sciences-related
Research InstitutionHokkaido University

Principal Investigator

Kikuchi Mani  北海道大学, 先端生命科学研究院, 博士研究員 (30788906)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords漢方 / 生薬 / 自然免疫 / Paneth細胞 / αディフェンシン / 腸内環境 / エンテロイド / α-defensin / 腸内細菌叢 / enteroid
Outline of Research at the Start

漢方で用いられる生薬は様々な症状に対して伝統的に用いられており、食による健康維持を考える上で重要な候補であるが、それらの生薬が症状を改善するメカニズムについては未だ明らかとなっていない。本研究はPaneth細胞の自然免疫機能に着目し、生薬の効能をPaneth細胞の顆粒分泌を介した腸内環境制御という視点から明らかにする。具体的には、腸の症状に有効とされる漢方、生薬について、小腸上皮組織の3次元培養系であるenteroid内腔へのマイクロインジェクションやマウスin vivo試験などにより、どのように腸内環境制御に関与するかを明らかにし、健康維持に有益な食材の発見や開発に貢献する。

Outline of Final Research Achievements

By focusing on innate immune function of small intestinal Paneth cells with the viewpoint of intestinal environment regulation, this study elucidates the mechanism for efficacy of Kampo herbal medicines which remains unknown, though, are important candidate food materials for maintaining health and preventing diseases. The Kampo herbs that induce alpha-defensin secretion were identified by the evaluation system for Paneth cell granule secretions using a three-dimensional ex vivo culture system of small intestinal epithelial cells, enteroid, further suggesting effects of Kampo herbs on improving the intestinal environment.

Academic Significance and Societal Importance of the Research Achievements

漢方・生薬は様々な症状に対して伝統的に用いられているが、それらが症状を改善するメカニズムは未だ不明の点が多い。本研究によって、漢方・生薬の効果を小腸のPaneth細胞が細胞内顆粒中に豊富に存在するαディフェンシンの分泌を誘導することを介する腸内環境の制御という視点からはじめて明らかにした。漢方・生薬の腸内環境に与える影響に関する全く新しいメカニズムを明らかにした本研究の学術的意義は大きく、さらに、本研究で得た腸内環境改善と健康維持に関する情報は新規食材開発に貢献する社会的意義を有する。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study2021

    • Author(s)
      Shimizu Yu、Nakamura Kiminori、Kikuchi Mani、Ukawa Shigekazu、Nakamura Koshi、Okada Emiko、Imae Akihiro、Nakagawa Takafumi、Yamamura Ryodai、Tamakoshi Akiko、Ayabe Tokiyoshi
    • Journal Title

      GeroScience

      Volume: - Issue: 2 Pages: 997-1009

    • DOI

      10.1007/s11357-021-00398-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Dynamics of Paneth cell granule secretory responses to bacteria in innate enteric immunity2021

    • Author(s)
      Yuki Yokoi, Kiminori Nakamura, Shuya Ohira, Ryuga Shinozaki, Mani Kikuchi, and Tokiyoshi Ayabe.
    • Organizer
      World Microbe Forum. Host-Microbe Biology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ER Stress-Associated Misfolding of Paneth Cell α-Defensin Induces Dysbiosis and Ileitis in a Murine Model of Crohn’s Disease2021

    • Author(s)
      Yu Shimizu, Kiminori Nakamura, Aki Yoshii, Yuki Yokoi, Mani Kikuchi, Ryuga Shinozaki, Shunta Nakamura, Shuya Ohira, Rina Sugimoto, and Tokiyoshi Ayabe.
    • Organizer
      World Microbe Forum. Host-Microbe Biology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Paneth細胞顆粒分泌応答からみた食機能評価系の確立2021

    • Author(s)
      横井友樹、中村公則、高桑暁子、菊池摩仁、綾部時芳.
    • Organizer
      第17回日本食品免疫学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 母親の高脂肪食摂取が子のPaneth細胞の発達に与える作用メカニズム2021

    • Author(s)
      八塚夏美、杉本理菜、大平修也、横井友樹、菊池摩仁、綾部時芳、中村公則.
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Simple and efficient genetic engineering of enteroids by using mouse isolated crypts2021

    • Author(s)
      Shuya Ohira, Yuki Yokoi, Mani Kikuchi, Natsumi Yatsuzuka, Tokiyoshi Ayabe, Kiminori Nakamura.
    • Organizer
      第44回日本分子生物学会年会 ワークショップ
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2023-01-30  

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