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Targeting gut microbiota as a novel therapy for asthma

Research Project

Project/Area Number 26560376
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionTohoku University

Principal Investigator

MIZUTA Kentaro  東北大学, 歯学研究科, 准教授 (40455796)

Co-Investigator(Kenkyū-buntansha) 正木 英二  東北大学, 歯学研究科, 教授 (40221577)
Research Collaborator Emala Charles W.  コロンビア大学, 医学部麻酔科学講座, 教授
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords気管支喘息 / 短鎖脂肪酸 / FFAR3 / 腸内細菌
Outline of Final Research Achievements

The incidence of asthma has increased greatly over the past decades. Hygiene hypotheses have suggested that the lack of exposure to microbial products in early life or the overuse of antibiotics would be the possible cause of this increase. Gut microbiota produces short-chain fatty acids (SCFAs), which acts on their sensors (FFAR2 and FFAR3 receptor). We investigated whether the receptors for SCFAs are expressed on human airway smith muscle, modulate airway smooth muscle tone, and induce airway remodeling. We detected the expression of FFAR3 in human airway smooth muscle. SCFAs potentiated airway smooth muscle contraction through inhibition of cAMP, while they did not induce airway remodeling. These results suggest that SCFAs stimulates FFAR3 receptor expressed on human airway smooth muscle, and modulates airway smooth muscle tone.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Int'l Joint Research] コロンビア大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] コロンビア大学(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia.2016

    • Author(s)
      Masaki E, Mizuta K, Ohtani N, Kido K
    • Journal Title

      Neurosignals

      Volume: 24 Pages: 15-24

    • DOI

      10.1159/000442608

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle2015

    • Author(s)
      Kentaro Mizuta, Yi Zhang, Fumiko Mizuta, Hiroshi Hoshijima, Toshiya Shiga, eiji Masaki, Charles W. Emala Sr.
    • Journal Title

      American Journal of Physiology Lung Cellular and Molecular Physiology

      Volume: 309 Issue: 9 Pages: L970-L982

    • DOI

      10.1152/ajplung.00041.2015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 遊離脂肪酸受容体を介した気管支喘息誘発機構2015

    • Author(s)
      水田健太郎
    • Journal Title

      BIO Clinica

      Volume: 30(9) Pages: 84-87

    • Related Report
      2015 Research-status Report
  • [Presentation] 短鎖脂肪酸による気管トーン調節機構2017

    • Author(s)
      水田健太郎、的場あつ子、正木英二、Charles W Emala
    • Organizer
      日本麻酔科学会 第64回学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2017-06-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 気管支痙攣と麻酔ー受容体と細胞内シグナリングを中心にー2016

    • Author(s)
      水田健太郎
    • Organizer
      第44回日本歯科麻酔学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-10-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 気管平滑筋における短鎖脂肪酸受容体FFAR3の発現と細胞内シグナリング機構2016

    • Author(s)
      水田健太郎、的場あつ子、松山奈央、水田文子、正木英二
    • Organizer
      第44回日本歯科麻酔学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-10-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] The Short Chain Free Fatty Acid Receptor FFAR3 is Expressed and Sensitizes cAMP Accumulation in Human Airway Smooth Muscle2016

    • Author(s)
      Kentaro Mizuta, Atsuko Matoba, Nao Matsuyama, Fumiko Mizuta, Eiji Masaki, Charles W. Emala
    • Organizer
      The Annual Meeting of American Society of Anesthesiologists 2016
    • Place of Presentation
      Chicago (USA)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ω-3遊離脂肪酸受容体FFAR4を介した気道リモデリング作用2015

    • Author(s)
      的場 あつ子、山本 奈央、堀 綾子、正木 英二、水田 健太郎
    • Organizer
      第43回日本歯科麻酔学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-31
    • Related Report
      2015 Research-status Report
  • [Presentation] オメガ3脂肪酸受容体FFAR4は気管の収縮・弛緩に関与するか?2015

    • Author(s)
      堀 綾子、的場 あつ子、正木 英二、水田 健太郎
    • Organizer
      第43回日本歯科麻酔学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-31
    • Related Report
      2015 Research-status Report
  • [Presentation] The free fatty acid receptor 1 promotes human airway smooth muscle cell proliferation through PI3K/Akt and MEK/ERK activation2015

    • Author(s)
      Kentaro Mizuta, Astuko Matoba, Ayako Hori, Nao Yamamoto, Eiji Masaki, Charles W. Emala
    • Organizer
      The annual meeting of American society of Anesthesiologist 2015
    • Place of Presentation
      SanDiego (USA)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 長鎖遊離脂肪酸受容体FFAR1 を介した気管平滑筋細胞増殖作用とその細胞内機序2015

    • Author(s)
      水田 健太郎
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      新潟市
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 長鎖遊離脂肪酸受容体による気道リモデリング促進作用の細胞内機序2015

    • Author(s)
      水田 健太郎、的場 あつ子、水田 文子、堀之内 節、佐藤 港、正木 英二
    • Organizer
      第62回日本麻酔科学会学術集会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 長鎖遊離脂肪酸による気道リモデリング促進作用の細胞内機序2015

    • Author(s)
      水田健太郎、的場あつ子、水田文子、堀之内節、佐藤港、正木英二
    • Organizer
      日本麻酔科学会第62回学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 遊離脂肪酸受容体FFAR1を介した気道リモデリング作用における細胞内シグナリング機構の解析2014

    • Author(s)
      的場あつ子、滝口晃嗣、正木英二、水田健太郎
    • Organizer
      第42回日本歯科麻酔学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2014-10-11 – 2014-10-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 脊髄性筋萎縮症Ⅲ型患者の全身麻酔経験2014

    • Author(s)
      山本奈央、水田健太郎、星島宏、正木英二
    • Organizer
      第42回日本歯科麻酔学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2014-10-11 – 2014-10-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 気管平滑筋に置ける遊離脂肪酸受容体FFAR1の発現と気管収縮促進作用2014

    • Author(s)
      水田健太郎
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2014-04-25 – 2014-04-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2022-02-16  

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