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Bidirectional signaling mechanism between the intestinal microbiota and brain: Molecular basis of obesity induced by stress.

Research Project

Project/Area Number 18K07879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKagawa University

Principal Investigator

Takanori Miki  香川大学, 医学部, 教授 (30274294)

Co-Investigator(Kenkyū-buntansha) 太田 健一  香川大学, 医学部, 助教 (50403720)
鈴木 辰吾  香川大学, 医学部, 准教授 (50451430)
横山 俊史  神戸大学, 農学研究科, 助教 (10380156)
割田 克彦  鳥取大学, 農学部, 准教授 (40452669)
金西 賢治  香川大学, 医学部, 教授 (10263906)
日下 隆  香川大学, 医学部, 教授 (50274288)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords母子分離 / 幼少期ストレス / 腸内細菌叢 / 炎症性サイトカイン / ミクログリア / 脳発達期ストレス / 炎症 / 内側前頭前皮質 / 発達障害 / ストレス曝露 / 脳発達 / サイトカイン / 脳 / 肥満 / ストレス / 生活習慣病 / 代謝調節 / 中枢神経 / 情報伝達
Outline of Final Research Achievements

Numerous studies reported on the effects of early life stress on brain and body development. However, little is known about how it alters the intestinal bacterial flora. The new vistas for understanding the brain-gut interactions related to the gut microbiota provide further insights to understanding the developmental mechanism of brain-gut interactions.
In this study, we examined the gut microbiota of a maternal separation model in rats and found changes in composition particularly related to lifestyle-related diseases and inflammation. Furthermore, this animal model showed an increased expression of inflammatory cytokines released by microglia in the brain during early life. These results suggest that early life stress alters an inflammation-prone gut microbiota, which may cause inflammation in the brain.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、幼少期ストレスが腸内細菌叢組成を変化させる事で生活習慣病及び脳内炎症を引き起こしやすい体内環境を生後早期の時点で作り上げてしまう事を示している。腸内細菌叢という観点から幼少期ストレスの影響を捉えようとする研究はまだ少ないが、この理解が進むことで育児放棄・虐待といった幼少期の不遇な養育環境にあった児のその後の発達を改善する手段として療育のみならず腸内細菌叢の改善という観点が産まれる。本研究結果を基盤に、更なる幼少期ストレスによる脳腸相関を原因とした影響が解明する事でそれを回復する機能性食品などの開発にも繋がる期待がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (24 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] ヤンゴン第一医科大学(ミャンマー)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ヤンゴン第一医科大学(ミャンマー)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Hypothermia cannot ameliorate renal fibrosis after asphyxia in the newborn piglet2022

    • Author(s)
      Wakabayashi Takayuki、Nakamura Shinji、Nakao Yasuhiro、Yamato Satoshi、Htun Yinmon、Mitsuie Tsutomu、Morimoto Aya、Arioka Makoto、Koyano Kosuke、Konishi Yukihiko、Miki Takanori、Ueno Masaki、Kusaka Takashi
    • Journal Title

      Pediatrics International

      Volume: 64 Issue: 1

    • DOI

      10.1111/ped.14961

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from <i>in vitro</i> transcriptomics2021

    • Author(s)
      Koshimizu Hisatsugu、Matsuoka Hidetada、Nakajima Yoshihiro、Kawai Anna、Ono Junichiro、Ohta Ken‐ichi、Miki Takanori、Sunagawa Masataka、Adachi Naoki、Suzuki Shingo
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 41 Issue: 4 Pages: 485-495

    • DOI

      10.1002/npr2.12208

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High Ethanol and Acetaldehyde Inhibit Glutamatergic Transmission in the Hippocampus of Aldh2-Knockout and C57BL/6N Mice: an In Vivo and Ex Vivo Analysis.2020

    • Author(s)
      Jamal M, Ito A, Tanaka N, Miki T, Ameno K, Kinoshita H.
    • Journal Title

      Neurotox Res.

      Volume: 37 Issue: 3 Pages: 702-713

    • DOI

      10.1007/s12640-020-00180-6

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meganuclease-Based Artificial Transcription Factors.2020

    • Author(s)
      Suzuki S, Ohta KI, Nakajima Y, Shigeto H, Abe H, Kawai A, Miura R, Kazuki Y, Oshimura M, Miki T.
    • Journal Title

      ACS Synth Biol.

      Volume: 16 Issue: 10 Pages: 2679-2691

    • DOI

      10.1021/acssynbio.0c00083

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of an organ culture system to induce Sertoli cell differentiation from undifferentiated mouse gonads2020

    • Author(s)
      HASEGAWA Chinatsu、YOKOYAMA Toshifumi、UMEMURA Yuria、KAWANISHI Kohei、MIURA Yuuka、TAKADA Nanako、OHNO Shuji、ONARU Kanoko、OMOTEHARA Takuya、HIRANO Tetsushi、MANTANI Yohei、Miki Takanori、HOSHI Nobuhiko
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 82 Issue: 4 Pages: 414-421

    • DOI

      10.1292/jvms.20-0036

    • NAID

      130007829882

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vexin is upregulated in cerebral cortical neurons by brain‐derived neurotrophic factor2020

    • Author(s)
      Hisatsugu Koshimizu, Shingo Suzuki, Anna Kawai, Ryuichiro Miura, Ken‐ichi Ohta, Takanori Miki, Naoki Adachi, Hidetada Matsuoka
    • Journal Title

      Neuropsychopharmacol Rep.

      Volume: 40 Issue: 3 Pages: 275-280

    • DOI

      10.1002/npr2.12119

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development2020

    • Author(s)
      Chiaki Tenkumo, Ken-ichi Ohta, Shingo Suzuki, Katsuhiko Warita, Kanako Irie, Saki Teradaya, Takashi Kusaka, Kenji Kanenishi, Toshiyuki Hata, Takanori Miki
    • Journal Title

      Heliyon

      Volume: 6 Issue: 8 Pages: e04781-e04781

    • DOI

      10.1016/j.heliyon.2020.e04781

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex2020

    • Author(s)
      Ohta KI, Suzuki S, Warita K, Sumitani K, Tenkumo C, Ozawa T, Ujihara H, Kusaka T, Miki T.
    • Journal Title

      Behav Brain Res

      Volume: 379 Pages: 112306-112306

    • DOI

      10.1016/j.bbr.2019.112306

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Partially hydrolyzed guar gum alleviates small intestinal mucosal damage after massive small bowel resection along with changes in the intestinal microbiota2019

    • Author(s)
      Fujii Takayuki、Chiba Yoichi、Nakayama-Imaohji Haruyuki、Onishi Shun、Tanaka Aya、Katami Hiroto、Kaji Tatsuru、Ieiri Satoshi、Miki Takanori、Ueno Masaki、Kuwahara Tomomi、Shimono Ryuichi
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 54 Issue: 12 Pages: 2514-2519

    • DOI

      10.1016/j.jpedsurg.2019.08.048

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model2019

    • Author(s)
      Htun Yinmon、Nakamura Shinji、Nakao Yasuhiro、Mitsuie Tsutomu、Nakamura Makoto、Yamato Satoshi、Jinnai Wataru、Koyano Kosuke、Ohta Kenichi、Morimoto Aya、Wakabayashi Takayuki、Sugino Masashiro、Fujioka Kazumichi、Kato Ikuko、Kondo Sonoko、Yasuda Saneyuki、Miki Takanori、Ueno Masaki、Kusaka Takashi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 4088-4088

    • DOI

      10.1038/s41598-019-40674-8

    • NAID

      120006599245

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic differences between C57BL/6 substrains affect the process of testis differentiation in Y<sup>POS</sup> mice2019

    • Author(s)
      YOKOYAMA Toshifumi、MIURA Yuuka、YAMAMOTO Anzu、HASEGAWA Chinatsu、KAWANISHI Kohei、TAKADA Nanako、OMOTEHARA Takuya、HIRANO Tetsushi、MANTANI Yohei、MIKI Takanori、HOSHI Nobuhiko
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 4 Pages: 608-611

    • DOI

      10.1292/jvms.18-0621

    • NAID

      130007638718

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] COA-Cl induces dopamine release and tyrosine hydroxylase phosphorylation: In vivo reverse microdialysis and in vitro analysis.2019

    • Author(s)
      Jamal M, Tsukamoto I, Takata M, Ito A, Tanaka N, Miki T, Takakura A, Ameno K, Kubota Y, Konishi R, Kinoshita H.
    • Journal Title

      Brain Res.

      Volume: 1706 Pages: 68-74

    • DOI

      10.1016/j.brainres.2018.10.026

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acetaldehyde administration induces salsolinol formation in vivo in the dorsal striatum of Aldh2-knockout and C57BL/6N mice.2018

    • Author(s)
      Ito A, Jamal M, Ameno K, Tanaka N, Takakura A, Kawamoto T, Kitagawa K, Nakayama K, Matsumoto A, Miki T, Kinoshita H.
    • Journal Title

      Neurosci Lett.

      Volume: 685 Pages: 50-54

    • DOI

      10.1016/j.neulet.2018.07.032

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between prolonged neural suppression and cerebral hemodynamic dysfunction during hypothermia in asphyxiated piglets.2018

    • Author(s)
      Jinnai W, Nakamura S, Koyano K, Yamato S, Wakabayashi T, Htun Y, Nakao Y, Iwase T, Nakamura M, Yasuda S, Ueno M, Miki T, Kusaka T
    • Journal Title

      Brain Dev

      Volume: 40 Issue: 8 Pages: 649-661

    • DOI

      10.1016/j.braindev.2018.04.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 母子分離による内側前頭前皮質におけるparvalbumin陽性抑制性ニューロンの減少2022

    • Author(s)
      本田航大、太田健一、入江加奈子、氏原英敏、鈴木辰吾、三木崇範
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脳由来神経栄養因子が発達期神経細胞の遺伝子発現に与える影響2020

    • Author(s)
      鈴木辰吾 太田健一 三木崇範
    • Organizer
      第125回日本解剖学会総会・全国学術集会 シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 脳発達期の母子分離が児の社会性に与える影響とその関連脳領域2020

    • Author(s)
      太田健一 鈴木辰吾 三木崇範
    • Organizer
      第125回日本解剖学会総会・全国学術集会 シンポジウム
    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Presentation] 4.脳由来神経栄養因子が発達期神経細胞の遺伝子発現に与える影響2020

    • Author(s)
      鈴木辰吾 太田健一 三木崇範
    • Organizer
      第125回日本解剖学会総会・全国学術集会 シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 養育環境は子供の脳を変える - 基礎医学研究からの知見 -2019

    • Author(s)
      三木崇範
    • Organizer
      第7回 新胎児学研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 新生仔豚仮死モデルにおける水素ガス吸入療法による脳保護効果について.2019

    • Author(s)
      中村信嗣, Yinmon Htun, 中尾泰浩, 光家努, 太田健一, 小谷野耕佑, 森本絢, 安田真之, 小西行彦, 加藤育子, 近藤園子, 三木崇範, 上野正樹, 日下隆.
    • Organizer
      平成30年度文部科学省新学術領域研究 学術研究支援基盤形成先端モデル動物支援プラットフォーム成果発表会
    • Related Report
      2018 Research-status Report
  • [Presentation] How can maternal deprivation cause developmental disorders?2019

    • Author(s)
      Ken-ichi Ohta, Singo Suzuki, Takanori Miki
    • Organizer
      9th Federation of the Asian and Oceanian Physiological Societies
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 母子分離による社会的認知能力の低下とその原因2018

    • Author(s)
      太田 健一、小澤 徹、鈴木 辰吾、三木 崇範
    • Organizer
      日本解剖学会第73回中国・四国支部学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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