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Elucidation of homeostatic mechanism via intestinal environment regulated by oral bacteria

Research Project

Project/Area Number 17K11661
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionHokkaido University

Principal Investigator

Nakamura Kiminori  北海道大学, 先端生命科学研究院, 准教授 (80381276)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords自然免疫 / Paneth細胞 / αディフェンシン / 免疫 / 感染 / 炎症
Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanism that commensal bacteria including oral bacteria and pathogenic bacteria are involved in the maintenance of intestinal homeostasis via interaction with Paneth cells. In this study, a novel ex vivo evaluation system to visualize and quantify Paneth cell granule secretion was established by microinjection method of bacteria into the lumen of enteroids, three-dimensional cultures of small intestinal epithelial cells. Paneth cells secreted granules immediately when live non-commensal bacterium S. Typhimurium or commensal bacterium B. bifidum was introduced into the enteroid lumen by microinjection, whereas Paneth cells did not secrete granules when live commensal bacterium L. casei was introduced.

Academic Significance and Societal Importance of the Research Achievements

本研究により樹立した共生細菌および病原菌に応答したPaneth細胞顆粒分泌評価システムは、Paneth細胞 αディフェンシンを中心とする新たな腸内細菌叢制御を介した生体恒常性維持のメカニズム解明を可能とする。この評価系により、口腔内を含む、様々な生体に共生する菌と腸管上皮細胞との相互作用を細胞・分子レベルで解析することにより、共生細菌と腸管のクロストークを介した恒常性の維持機構が明らかとなり、共生細菌と宿主のバランスの破綻が原因の一つと考えられている、生活習慣病などに対する新たな予防・治療戦略の提案が期待できる。

Report

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

    (22 results)

All 2020 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Analysis of Serotonin in Human Feces Using Solid Phase Extraction and Column-Switching LC-MS/MS2020

    • Author(s)
      Hirabayashi Y, Nakamura K, Sonehara T, Suzuki D, Hanzawa S, Shimizu Y, Aizawa T, Nakamura K, Tamakoshi A, Ayabe T
    • Journal Title

      Mass Spectrometry

      Volume: 9 Issue: 1 Pages: A0081-A0081

    • DOI

      10.5702/massspectrometry.A0081

    • NAID

      130007823248

    • ISSN
      2186-5116, 2187-137X
    • Year and Date
      2020-03-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of gut microbiota, dietary intake, and serum short-chain fatty acids with fecal short-chain fatty acids2020

    • Author(s)
      Yamamura R, Nakamura K, Kitada N, Aizawa T, Shimizu Y, Nakamura K, Ayabe T, Kimura T, Tamakoshi A
    • Journal Title

      Bioscience of Microbiota, Food and Health

      Volume: 39 Issue: 1 Pages: 11-17

    • DOI

      10.12938/bmfh.19-010

    • NAID

      130007788976

    • ISSN
      2186-3342
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Butyric Acid and Leucine Induce α-Defensin Secretion from Small Intestinal Paneth Cells2019

    • Author(s)
      Takakuwa Akiko、Nakamura Kiminori、Kikuchi Mani、Sugimoto Rina、Ohira Shuya、Yokoi Yuki、Ayabe Tokiyoshi
    • Journal Title

      Nutrients

      Volume: 11 Issue: 11 Pages: 2817-2817

    • DOI

      10.3390/nu11112817

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A simple culture method for liver and intestinal tissue-resident macrophages from neonatal mice2019

    • Author(s)
      Shimizu Y, Sakuragi N, Nakamura K, Taira T, Ayabe T, Fukui A
    • Journal Title

      In Vitro Cell Dev Biol - Animal

      Volume: 55 Issue: 6 Pages: 436-444

    • DOI

      10.1007/s11626-019-00359-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway.2019

    • Author(s)
      Pillai MR, Mihi B, Ishiwata K, Nakamura K, Sakuragi N, Finkelstein DB, McGargill MA, Nakayama T, Ayabe T, Coleman ML, Bix M
    • Journal Title

      PLoS One

      Volume: 26;14(2):e0211244 Issue: 2 Pages: 1-21

    • DOI

      10.1371/journal.pone.0211244

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.2018

    • Author(s)
      Yaguchi K, Yamamoto T, Shimada M, Sugimoto R, Nakamura K, Ayabe T, Uehara R.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 504 Issue: 1 Pages: 231-231

    • DOI

      10.1016/j.bbrc.2018.08.160

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Essential role of IFN-γ in T cell?associated intestinal inflammation2018

    • Author(s)
      Eriguchi Yoshihiro、Nakamura Kiminori、Yokoi Yuki、Sugimoto Rina、Takahashi Shuichiro、Hashimoto Daigo、Teshima Takanori、Ayabe Tokiyoshi、Selsted Michael E.、Ouellette Andre J.
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 18 Pages: 1-18

    • DOI

      10.1172/jci.insight.121886

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Entamoeba histolytica Alters ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency.2018

    • Author(s)
      Cobo ER, Holani R, Moreau F, Nakamura K, Ayabe T, Mastroianni JR, Eriguchi Y, Ouellette A, Chadee K
    • Journal Title

      Infect Immiune

      Volume: 21;86(10) Issue: 10

    • DOI

      10.1128/iai.00564-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease2017

    • Author(s)
      Hayase E, Hashimoto D, Nakamura K, Noizat C, Ogasawara R, Takahashi S, Ohigashi H, Yokoi Y, Sugimoto R, Matsuoka S, Ara T, Yokoyama E, Yamakawa T, Ebata K, Kondo T, Hiramine R, Aizawa T, Ogura Y, Hayashi T, Mori H, Kurokawa K, Tomizuka K, Ayabe T, Teshima T
    • Journal Title

      J Exp Med

      Volume: 214 Issue: 12 Pages: 3507-3518

    • DOI

      10.1084/jem.20170418

    • NAID

      120006394569

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 多様なα-defensin isoformに対するin vitroにおける効率的なS-S結合導入法の確立2019

    • Author(s)
      篠崎 竜我、中村 公則、清水 由宇、綾部 時芳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 母親の高脂肪食摂取が子の腸管上皮幹細胞ニッシェに与える影響2019

    • Author(s)
      嶋 七海、中村 公則、杉本 理菜、横井 友樹、綾部 時芳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Acetylcholine-induced Paneth Cell Granule Secretion Via Muscarinic M3 Receptor In Mouse Small Intestine2019

    • Author(s)
      Yuki Yokoi, Kiminori Nakamura, Rina Sugimoto, Shuya Ohira, Mani Kikuchi, Tokiyoshi Ayabe
    • Organizer
      ASCB EMBO 2019 Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Paneth cell dysfunction in pathophysiology of nonalcoholic steatohepatitis.2019

    • Author(s)
      Shunta Nakamura, Kiminori Nakamura, Mani Kikuchi, Yuki Yokoi, Shuya Ohira, Yu Shimizu, Takuto Nishida, Tokiyoshi Ayabe
    • Organizer
      ASCB EMBO 2019 Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 母親の高脂肪食摂取が子のPaneth細胞α-defensinによる腸内環境制御に与える影響2019

    • Author(s)
      杉本 理菜、中村 公則、嶋 七海、清水 由宇、横井 友樹、綾部 時芳
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Involvement of Paneth cell alpha-defensin misfolding in disease progression of SAMP1/YitFc, a murine model of Crohn's disease.2018

    • Author(s)
      Yu Shimizu, Kiminori Nakamura, Mani Kikuchi, Tokiyoshi Ayabe
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] レスベラトロール摂取によるα-defensin 分泌量と腸内細菌叢への影響2018

    • Author(s)
      中村 公則、杉本 理菜、横井 友樹、清水 由宇、菊池 摩仁、綾部 時芳
    • Organizer
      日本食品免疫学会 第14回 学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸管organoidを用いたPaneth細胞分化制御機構の解析2018

    • Author(s)
      大平 修也、中村 公則、菊池 摩仁、横井 友樹、杉本 理菜、綾部 時芳
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Enteroidを用いたPaneth細胞が制御する腸内環境の機能解明2018

    • Author(s)
      中村 公則、横井 友樹、米田 司、綾部 時芳
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 高純度ソーティング由来cDNAライブラリーを用いたPaneth細胞の新規機能探索2017

    • Author(s)
      櫻木 直也、中村 公則、 横井 友樹、菊池 摩仁、綾部 時芳
    • Organizer
      日本食品免疫学会第13回学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Enteroid内腔へのマイクロインジェクションによるPaneth細胞顆粒分泌評価システムの確立と応用2017

    • Author(s)
      米田 司、中村 公則、横井 友樹、大平 修也、菊池 摩仁、櫻木 直也、綾部 時芳
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] クローン病モデルマウスSAMP1/YitFcにおけるPaneth細胞α-defensinのmisfolding2017

    • Author(s)
      清水 由宇、中村 公則、菊池 摩仁 、櫻木 直也、綾部 時芳
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Evaluation system for receptor expression and function in the intestinal stem cell niche2017

    • Author(s)
      Rina Sugimoto, Naoya Sakuragi, Yuki Yokoi, Kiminori Nakamura, Tokiyoshi Ayabe
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report

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

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