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Comprehensive metagenomic analysis of intestinal bacterial and viral flora in Alzheimer's disease

Research Project

Project/Area Number 19K17028
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionOsaka Metropolitan University (2022)
Osaka City University (2019-2021)

Principal Investigator

Uematsu Miho  大阪公立大学, 大学院医学研究科, 助教 (80815647)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsメタゲノム解析 / メタボローム解析 / 腸内細菌叢 / 腸内ウイルス叢 / アルツハイマー型認知症 / パーキンソン病関連疾患 / KEGG / 次世代シークエンサー / 遺伝子機能解析 / メタゲノム / 腸内微生物叢 / パーキンソン病 / アルツハイマー病 / 次世代シーケンサー
Outline of Research at the Start

近年、腸内微生物叢が腸脳相関を介して神経変性疾患の病態に影響を与える可能性を示唆する報告が続いている。一方、viral dark matterと呼ばれる腸内ウイルス叢のゲノム配列や機能、種々の疾患との関係については、ほとんど分かっていない。本研究では、アルツハイマー病とパーキンソン病患者の糞便サンプルを用いて、細菌叢およびウイルス叢を含む腸内微生物叢の全ゲノム解析を行い、さらに同定された遺伝子を機能データベース(KEGG)で相同検索して機能解析を行う。これにより、神経変性疾患で蓄積する異常な蛋白の修飾や代謝調節に関わる可能性のある分子を探索して、腸内環境調整による新たな治療アプローチを見出す。

Outline of Final Research Achievements

In recent years, it has been suggested that the gut microbiota may influence the pathogenesis of neurodegenerative diseases via the gut-brain connection. On the other hand, little is known about the genome sequence and function of the gut viral flora, called viral dark matter, and its relationship with various diseases. In this study, we focused on Alzheimer's disease and Parkinson's disease, which are thought to be strongly influenced by the gut-brain connection. After extracting the genes of intestinal bacteria and viruses from fecal samples, the genome sequences were analyzed using a next-generation sequencer and a supercomputer. Comparison of the metagenomes of the bacterial and viral flora in the disease and healthy control groups showed that the composition of the microflora and gene function differed between the disease and healthy control groups. This finding indicated that gut dysbiosis could be a potential target for novel therapies for neurodegenerative diseases.

Academic Significance and Societal Importance of the Research Achievements

近年、次世代シークエンサー技術の飛躍的な進歩に伴い、腸内細菌叢の組成やその代謝産物が疾患の発症に与える影響に特に注目が集まっている。とりわけ、神経変性疾患と脳腸相関の関係は世界的に注目されている。本研究では、神経変性疾患に特徴的な腸内細菌叢の組成異常(ディスバイオシス)と遺伝子機能の変化を網羅的に解析することで、神経変性疾患の治療法を検討した。本研究のように腸内細菌叢の遺伝子機能を解析することで見出される治療戦略は、今後、新たな治療介入につながると期待される。

Report

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

    (9 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results)

  • [Journal Article] Parallel gold enhancement of quantum dots 565/655 for double-labelling correlative light and electron microscopy on human autopsied samples.2022

    • Author(s)
      Uematsu M, Mikami K, Nakamura A, Takahashi R, Yokota T, Hirokawa K, Uchihara T
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 12 Issue: 1 Pages: 6113-6113

    • DOI

      10.1038/s41598-022-09849-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation2021

    • Author(s)
      Fujimoto, Kosuke, et al.
    • Journal Title

      Gastroenterology

      Volume: - Issue: 6 Pages: 400-405

    • DOI

      10.1053/j.gastro.2021.02.013

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts2020

    • Author(s)
      Fujimoto Kosuke、Kimura Yasumasa、Shimohigoshi Masaki、Satoh Takeshi、Sato Shintaro、Tremmel Georg、Uematsu Miho、Kawaguchi Yunosuke、Usui Yuki、Nakano Yoshiko、Hayashi Tetsuya、Kashima Koji、Yuki Yoshikazu、Yamaguchi Kiyoshi、Furukawa Yoichi、Kakuta Masanori、Akiyama Yutaka、Yamaguchi Rui、Crowe Sheila E. et al
    • Journal Title

      Cell Host & Microbe

      Volume: 28 Issue: 3 Pages: 380-389

    • DOI

      10.1016/j.chom.2020.06.005

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases2019

    • Author(s)
      Fujimoto Kosuke、Kawaguchi Yunosuke、Shimohigoshi Masaki、Gotoh Yoshiyuki、Nakano Yoshiko、Usui Yuki、Hayashi Tetsuya、Kimura Yasumasa、Uematsu Miho、Yamamoto Takuya、Akeda Yukihiro、Rhee Joon Haeng、Yuki Yoshikazu、Ishii Ken J.、Crowe Sheila E.、Ernst Peter B.、Kiyono Hiroshi、Uematsu Satoshi
    • Journal Title

      Gastroenterology

      Volume: 157 Issue: 6 Pages: 1530-1543

    • DOI

      10.1053/j.gastro.2019.08.021

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] How to demix Alzheimer-type and PSP-type tau lesions out of their mixture -hybrid approach to dissect comorbidity-2019

    • Author(s)
      Momoko Ebashi, Yoshinori Ito, Miho Uematsu, Ayako Nakamura, Katsuiku Hirokawa, Satoshi Kamei and Toshiki Uchihara
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 7 Issue: 1 Pages: 71-71

    • DOI

      10.1186/s40478-019-0708-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ホットトピックス06 プロテイノパチー克服への道程:タウオパチーの病理学的検討と新規治療法の開発2020

    • Author(s)
      植松未帆
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] シンポジウム3 タウ病変の疾患特異性ー臨床診断から分子基盤までー:タウ分子が織りなす超微形態、病変と分布からヒト脳疾患まで2020

    • Author(s)
      植松未帆
    • Organizer
      第61回日本神経病理学会総会学術研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Quantum dot/nanogold colabeling for double correlative light and electron microscopy of human brain2020

    • Author(s)
      植松未帆
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] AD特異的4Rタウ病変をPSPと区別する2019

    • Author(s)
      江橋 桃子、融 衆太、伊藤 嘉憲、植松 未帆、中村 綾子、亀井 聡、横田 隆徳、廣川 勝昱、 内原 俊記
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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