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Development of therapy for improving liver regeneration disorders associated with obstructive jaundice through intestinal microbiota metagenome analysis

Research Project

Project/Area Number 20K09101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionShinshu University

Principal Investigator

Shimizu Akira  信州大学, 学術研究院医学系(医学部附属病院), 准教授 (00447773)

Co-Investigator(Kenkyū-buntansha) 副島 雄二  信州大学, 学術研究院医学系, 教授 (30325526)
安川 紘矢  信州大学, 医学部, 特任助教 (30868071)
野竹 剛  信州大学, 学術研究院医学系(医学部附属病院), 助教 (40645511)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腸内細菌叢 / 胆汁鬱滞モデル / 肝切除 / メタゲノム解析 / 肝再生 / 胆汁鬱滞
Outline of Research at the Start

我々は,腸内細菌叢と肝再生能力との関連に着目し以下のことを研究期間内に明らかにする.
①閉塞性黄疸患者の腸内細菌叢の特徴,②胆汁還元に伴う腸内細菌叢の変化,③胆汁鬱滞ラットモデルを用いた腸内細菌叢解析と細菌叢(便)移植による肝再生能力改善効果,④80%肝切除付加胆汁鬱滞ラットモデルにおける腸内細菌叢移植とシンバイオティクスによる肝再生能力改善効果,⑤①から④で得られた知見を元に,閉塞性黄疸・胆汁鬱滞肝に対して有効な肝再生促進治療法の開発を行い,その効果を検証する.

Outline of Final Research Achievements

Based on the hypothesis that obstructive jaundice with biliary stasis, which causes dramatic changes in the enterohepatic circulation, disrupts the gut microbiota and impairs liver regeneration capacity, we conducted the following study.
We created a biliary stasis model using common bile duct ligation and compared the gut microbiota diversity with a control model. As a result, while a difference in alpha diversity was observed on Day 4 in the biliary stasis model, no significant changes in beta diversity were confirmed at each time point between the control and biliary stasis models.
Additionally, models with 80% hepatectomy added to both the control and biliary stasis models were created. When comparing the ratio of remnant liver weight to total liver weight on postoperative day 2, no significant difference was observed as initially expected.

Academic Significance and Societal Importance of the Research Achievements

胆汁鬱滞という腸肝循環に大きな変化と影響を及ぼす病態における腸内細菌叢の変化について、その一端を明らかにすることができたが、コントロールと比較して著明な細菌叢変化を生じている証拠を明らかにすることはできず、また肝再生抑制効果に関しても検証は不十分であり、今後の課題と考えられた。

Report

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

    (1 results)

All 2023

All Journal Article (1 results)

  • [Journal Article] 腸内細菌は閉塞性黄疸により影響されるのか2023

    • Author(s)
      増尾仁志, 清水明, 生井楓, 副島雄二
    • Journal Title

      胆と膵

      Volume: 44 Pages: 223-227

    • Related Report
      2022 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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