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Analysis of mechanism for dietary emulsifying agents caused intestinal inflammatory

Research Project

Project/Area Number 19K05875
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionNational Defense Medical College

Principal Investigator

Kurihara Chie  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 内科学, 助教 (90532515)

Co-Investigator(Kenkyū-buntansha) 穂苅 量太  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 内科学, 教授 (90255464)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords乳化剤 / 腸内細菌 / 炎症性腸疾患 / 腸内細菌叢 / 腸管炎症
Outline of Research at the Start

炎症性腸疾患 (IBD) は原因不明の難治性疾患であるが、病因の一つとして食べ物や腸内細菌などの環境的要因による消化管免疫バランスの破綻が想定されている。近年、加工食品用添加物の一つである乳化剤が、動物モデルの腸内細菌叢を変化させ、腸炎を引き起こすことが報告された。本研究では、乳化剤がどのような機序で腸内環境バランスを破壊し腸炎を誘発するのかを解明し、IBDの予防や治療に結びつけることを目指す。

Outline of Final Research Achievements

The effect of dietary emulsifiers on small-intestinal microbiota, which is important for gut immunity, has not been studied. We investigated the effect of a dietary emulsifier, polysorbate-80 (P80), on the small intestine in normal mice and Indomethacin-induced inflammation model mice. P80 reduced the microbiota diversity, especially in the small intestine rather than in the colon, in normal mice. And P80 increased the number of sulfide-producing Enterobacteriaceae in small-intestinal mucosa, which was identified as P. mirabilis. P80 alone did not cause small-intestinal injury of normal mice, but exacerbated indomethacin-induced intestinal lesions. We showed that P80 induced dysbiosis in the small intestine, leading to enhanced vulnerability of the small intestine to indomethacin-induced injury. Also, we showed that another kind of emulsifier ingestion changed diversity of the gut microbiota. However, degree of risk for gut damage varied by type of emulsifiers.

Academic Significance and Societal Importance of the Research Achievements

近年の炎症性腸疾患患者数増加の一因として、乳化剤摂取量の増加が指摘されている。本研究において、乳化剤摂取による腸内細菌叢の撹乱(dysbiosis)が小腸炎を起こしやすい環境を作っていること、また腸管粘膜バリア損傷の程度は乳化剤の種類によって異なることを明らかにした。これらの成果は、今後の炎症性腸疾患の発症予防や食事指導による治療につながることが期待でき、社会に貢献ができると考えている。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (9 results) (of which Int'l Joint Research: 7 results)

  • [Journal Article] リンパ球マイグレーションを変化させる管腔内因子2022

    • Author(s)
      東山正明, 澁谷尚希, 塙芳典, 古橋廣崇, 栗原千枝, 穂苅量太
    • Journal Title

      リンパ学

      Volume: 45(2) Pages: 100-103

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa2021

    • Author(s)
      Hanawa Yoshinori、Higashiyama Masaaki、Kurihara Chie、Tanemoto Rina、Ito Suguru、Mizoguchi Akinori、Nishii Shin、Wada Akinori、Inaba Kenichi、Sugihara Nao、Horiuchi Kazuki、Okada Yoshikiyo、Narimatsu Kazuyuki、Komoto Shunsuke、Tomita Kengo、Hokari Ryota
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 36 Issue: 11 Pages: 3140-3148

    • DOI

      10.1111/jgh.15654

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal inflammations increase efflux of innate lymphoid cells from the intestinal mucosa to the mesenteric lymph nodes through lymph-collecting ducts2021

    • Author(s)
      Kazuki Horiuchi, Masaaki Higashiyama, Chie Kurihara, Kouji Matsumura, Rina Tanemoto, Suguru Ito, Akinori Mizoguchi, Shin Nishii, Akinori Wada, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Kengo Tomita, Ryota Hokari
    • Journal Title

      Microcirculation

      Volume: - Issue: 5

    • DOI

      10.1111/micc.12694

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective Effect of Luminal Uric acid Against Indomethacin-induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota2021

    • Author(s)
      Wada A; Higashiyama M.; Kurihara C.; Ito S.; Tanemoto R.; Mizoguchi A.; Nishii S.;Inaba K.; Sugihara N.; Hanawa .Y; Horiuchi K.; Shibuya N.; Akiyama M.; Okada Y.; Watanabe C.; Komoto S.; Tomita K.; Takei F.; Hokari R.
    • Journal Title

      Digestive Diseases and Sciences.

      Volume: in press Issue: 1 Pages: 121-133

    • DOI

      10.1007/s10620-021-06848-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dietary emulsifier polysorbate‐80‐induced small‐intestinal vulnerability to indomethacin‐induced lesions via dysbiosis2019

    • Author(s)
      Furuhashi Hirotaka、Higashiyama Masaaki、Okada Yoshikiyo、Kurihara Chie、Wada Akinori、Horiuchi Kazuki、Hanawa Yoshinori、Mizoguchi Akinori、Nishii Shin、Inaba Kenichi、Sugihara Nao、Watanabe Chikako、Komoto Shunsuke、Tomita Kengo、Miura Soichiro、Hokari Ryota
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 35 Issue: 1 Pages: 110-117

    • DOI

      10.1111/jgh.14808

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] THE IMPACT OF DIETARY EMULSIFIERS ON CHANGES OF MOUSE GUT MICROBIOTA AND INCREASED INTESTINAL PERMEABILITY DEPENDS ON HYDROPHILIC-LIPOPHILIC BALANCE2023

    • Author(s)
      Chie Kurihara, Masaaki Higashiyama, Yuta Yoshidome, Hiroyuki Tahara, Kana Ayaki, Hiroyuki Nishimura, Akira Tomioka, Suguru Ito, Rina Tanemoto, Yoshikiyo Okada, Kazuyuki Narimatsu, Shunsuke Komoto, Kengo Tomita, Ryota Hokari
    • Organizer
      Digestive Disease Week 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] THERAPEUTIC EFFICACY OF GRANULOCYTE AND MONOCYTE ADSORPTIVE APHERESIS IS CORRELATED WITH COLONIC MUCOSAL EXPRESSION OF TIGHT JUNCTION MOLECULES IN ULCERATIVE COLITIS2021

    • Author(s)
      Chie Kurihara, Toshihide Ohmori, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Kazuki Horiuch, Akinori Wada, Shin Nishii, Akinori Mizoguchi, Suguru Ito, Rina Tanemoto, Akira Tomioka, Yoshikiyo Okada, Akita Yoshihiro, Narimatsu Kazuyuk, Higashiyama Masaaki, Shunsuke Komoto, Kengo Tomita, Ryota Hokar
    • Organizer
      Digestive Disease Week 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食品添加物として用いられる微量の乳化剤が腸粘膜バリアに与える影響について2021

    • Author(s)
      穂苅量太
    • Organizer
      第48回日本潰瘍学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Analysis of dietary emulsifier leading to change diversity of the gut microbiota and increased intestinal permeability2020

    • Author(s)
      Chie Kurihara, Akinori Wada, Hirotaka Furuhashi, Masaaki Higashiyama, Ryota Hokari
    • Organizer
      The 8th Annual Meeting of Asian Organization for Crohn's and Colitis (AOCC2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] DEOXYCHOLIC ACID ENHANCES INTESTINAL LYMPHOCYTE MIGRATION TO VASCULAR ENDOTHELIUM BY DIRECT INCREASE IN EXPRESSIONS OF ICAM-I AND VCAM-1 THROUGH SPHINGOSINE-1-PHOSPHATE RECEPTOR 22020

    • Author(s)
      Naoki Shibuya, Masaaki Higashiyama, Shin Nishii, Akinori Mizoguchi, Chie Kurihara, Ryota Hokari
    • Organizer
      Digestive Disease Week 2020,
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efficacy of Granulocyte and Monocyte Adsorptive Apheresis Treatment is Correlated with Colonic Mucosal Expression of Th17-asociated Cytokines in Ulcerative Colitis2020

    • Author(s)
      Chie Kurihara, Toshihide Ohmor, iKenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Kazuki Horiuchi, Ryota Hokari
    • Organizer
      Digestive Disease Week 2020,
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳化剤が腸管自然リンパ球に及ぼす影響の検討2019

    • Author(s)
      堀内和樹、東山正明、西井慎、溝口明範、因幡健一、杉原奈央、塙芳典、和田晃典、古橋廣崇、澁谷尚希、栗原千枝、岡田義清、渡辺知佳子、高本俊介、冨田謙吾、穂苅量太
    • Organizer
      第43回日本リンパ学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] DISTINCTIVE SUBPOPULATION OF INNATE LYMPHOID CELLS EFFLUXED FROM INTESTINAL MUCOSA BY DIFFERENT INTESTINAL INFLAMMATIONS2019

    • Author(s)
      Kazuki Horiuchi, Masaaki Higashiyama, Koji Matsumura, Hiroshi Ohno, Shin Nishii, Akinori Mizoguchi, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Akinori Wada, Hirotaka Furuhashi, Naoki Shibuya, Chie Kurihara, Yoshikiyo Okada, Hideaki Hozumi, Chikako Watanabe, Shunsuke Komoto, Kengo Tomita, Ryota Hokari
    • Organizer
      Digestive Disease Week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Higher TNFα and MIP-1β expression in pretreatment colonic mucosa have potential to predict of achieving mucosal healing by GMA therapy in ulcerative colitis patients2019

    • Author(s)
      Chie Kurihara, Toshihide Ohmori, Hirotaka Furuhashi, IKenichi naba ,Nao Sugihara, Yoshinori Hanawa, Kazuki Horiuchi, Akinori Wada, Shin Nishii, Akinori Mizoguchi, Yoshikiyo Okada, Naoki Shibuya, Hideaki Hozumi, Masaaki Higashiyama, Chikako Watanabe, Shunsuke Komoto, Kengo Tomita ,Ryota Hokari
    • Organizer
      Digestive Disease Week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2025-01-30  

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