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Reconstruction of metabolism in sepsis by targeting gut microbiota

Research Project

Project/Area Number 21H03033
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionKumamoto University

Principal Investigator

ITO Takashi  熊本大学, 大学院生命科学研究部(保), 教授 (20381171)

Co-Investigator(Kenkyū-buntansha) 丸山 征郎  鹿児島大学, 医歯学総合研究科, 客員研究員 (20082282)
垣花 泰之  鹿児島大学, 医歯学域医学系, 教授 (20264426)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords敗血症 / 腸内細菌 / メタボローム / 腸内細菌叢
Outline of Research at the Start

我々は本申請に先立つ代謝産物の網羅的な解析において、敗血症によって増加する代謝産物以外に、減少する代謝産物が数多く存在し、そのなかでも特に、腸内細菌によるナイアシン類の産生が顕著に減少することを見出した。さらに、腸内細菌を制御しうる希少糖を用いてナイアシン類産生を改善させると、敗血症モデルマウスの生存率を有意に改善できることを見出した。本研究では、敗血症-腸内細菌叢の攪乱-ナイアシン産生障害を基軸とした敗血症の新規病態生理を実証するとともに、それをもとにした新規治療戦略の構築を目指す。

Outline of Final Research Achievements

In this study, we tried to clarify the pathogenesis of sepsis and develop a new treatment strategy. We found that tryptophan metabolites were decreased in serum of mice with sepsis. Furthermore, genes of gut microbes required for tryptophan metabolism were also decreased in mice with sepsis. Supplementation with prebiotics that can increase tryptophan metabolism improved the survival of mice with sepsis. These findings provide new insight into the pathogenesis and treatment option for sepsis.

Academic Significance and Societal Importance of the Research Achievements

敗血症は、感染に対する制御不能な生体反応によって引き起こされる生命を脅かすような臓器障害と定義されている。本邦では年間30万人以上が敗血症となり、そのうちおよそ1/5が死亡していると言われている。敗血症の治療は、微生物感染に対する抗菌薬等の投与、臓器障害に対する臓器支持療法が中心で、制御不能な生体反応に対する理解と治療介入手段は現状で乏しい。本研究の成果は、そのような敗血症時の生体反応に関する理解を深め、新規治療オプションを提案することによって、敗血症の生存率を向上させるための礎となる可能性を秘めている。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (20 results)

All 2024 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (12 results) (of which Invited: 5 results) Book (1 results)

  • [Journal Article] Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis2024

    • Author(s)
      Totoki Takaaki、Makino Yuto、Yamakawa Kazuma、Koami Hiroyuki、Wada Takeshi、Ito Takashi、Iba Toshiaki
    • Journal Title

      Thrombosis Journal

      Volume: 22 Issue: 1 Pages: 10-10

    • DOI

      10.1186/s12959-023-00579-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Damage-associated molecular patterns and fibrinolysis perturbation are associated with lethal outcomes in traumatic injury.2023

    • Author(s)
      Shimono K, Ito T, Kamikokuryo C, Niiyama S, Yamada S, Onishi H, Yoshihara H, Maruyama I, Kakihana Y.
    • Journal Title

      Thromb J

      Volume: 21(1) Issue: 1 Pages: 91-91

    • DOI

      10.1186/s12959-023-00536-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticoagulation therapy for microvascular dysfunction2023

    • Author(s)
      TOTOKI Takaaki、ITO Takashi
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 34 Issue: 6 Pages: 671-678

    • DOI

      10.2491/jjsth.34.671

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early ascorbic acid administration prevents vascular endothelial cell damage in septic mice2022

    • Author(s)
      Yutaro Madokoro, Chinatsu Kamikokuryo, Shuhei Niiyama, Takashi Ito, Satoshi Hara, Hiroshi Ichinose, Yasuyuki Kakihana
    • Journal Title

      Frontiers in Pharmacology

      Volume: - Pages: 929448-929448

    • DOI

      10.3389/fphar.2022.929448

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Attempt for a Recombinant Thrombomodulin Alpha Treatment in a Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom2022

    • Author(s)
      Yamamoto Akihiko、Ito Takashi、Hifumi Toru
    • Journal Title

      Toxins

      Volume: 14 Issue: 5 Pages: 322-322

    • DOI

      10.3390/toxins14050322

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential roles of 1,5-anhydro-d-fructose in modulating gut microbiome in mice2021

    • Author(s)
      Ito Takashi、Totoki Takaaki、Takada Seiya、Otsuka Shotaro、Maruyama Ikuro
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 19648-19648

    • DOI

      10.1038/s41598-021-99052-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating Syndecan-1 as a Predictor of Persistent Thrombocytopenia and Lethal Outcome: A Population Study of Patients With Suspected Sepsis Requiring Intensive Care2021

    • Author(s)
      Hatanaka Kosaku、Ito Takashi、Madokoro Yutaro、Kamikokuryo Chinatsu、Niiyama Shuhei、Yamada Shingo、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 8 Pages: 730553-730553

    • DOI

      10.3389/fcvm.2021.730553

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 敗血症性臓器障害のメカニズムを紐解く ―DAMPsおよびNETsの関与を考える―2024

    • Author(s)
      伊藤隆史
    • Organizer
      第51回日本集中治療医学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 基礎研究から考える敗血症性DICの病態と治療2023

    • Author(s)
      伊藤隆史
    • Organizer
      第45回日本血栓止血学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 今あらためて考えるCOVID-19重症化2023

    • Author(s)
      伊藤隆史
    • Organizer
      第45回日本血栓止血学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 血管内における炎症と凝固のクロストーク2023

    • Author(s)
      伊藤隆史
    • Organizer
      第43回日本川崎病学会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 血管内恒常性維持とトロンボモジュリン2023

    • Author(s)
      伊藤隆史
    • Organizer
      第22回日本血管血流学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 炎症と凝固のクロストーク 侵襲に対する原始応答の生理と病理2022

    • Author(s)
      伊藤隆史
    • Organizer
      第69回日本麻酔科学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞の抗血栓性と血管内凝固2022

    • Author(s)
      伊藤隆史
    • Organizer
      第44回日本血栓止血学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 敗血症性DICにおける臓器障害/予後予測因子としてのcirculating histone H32022

    • Author(s)
      伊藤隆史
    • Organizer
      第23回日本検査血液学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 血流下での血小板機能解析の意義と可能性2022

    • Author(s)
      伊藤隆史
    • Organizer
      第62回日本臨床化学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 敗血症/無菌性炎症におけるDAMPsの動態と病態2022

    • Author(s)
      伊藤隆史
    • Organizer
      第50回日本救急医学会総会・学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 侵襲応答と臓器障害 up-to-date2021

    • Author(s)
      伊藤隆史
    • Organizer
      第49回日本集中治療医学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 敗血症-好中球-ヒストン-DIC 連関の基礎と臨床2021

    • Author(s)
      伊藤隆史
    • Organizer
      第49回日本集中治療医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Book] 集中治療医学2023

    • Author(s)
      編集:一般社団法人日本集中治療医学会 分担執筆:伊藤隆史
    • Total Pages
      424
    • Publisher
      Gakken
    • ISBN
      4055100248
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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