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Mechanism of liver fibrosis progression in severely obese patients investigated by changes of bacterial flora and multiomics analysis

Research Project

Project/Area Number 22K11812
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionIwate Medical University

Principal Investigator

Umemura Akira  岩手医科大学, 医学部, 准教授 (10749675)

Co-Investigator(Kenkyū-buntansha) 佐々木 章  岩手医科大学, 医学部, 教授 (40275540)
柿坂 啓介  岩手医科大学, 医学部, 准教授 (40583563)
石垣 泰  岩手医科大学, 医学部, 教授 (50375002)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords高度肥満症 / 減量・代謝改善手術 / ケトン体 / 異所性脂肪 / 腸内細菌 / 口腔内細菌 / オミックス解析 / メタボローム解析 / 非アルコール性脂肪性肝炎 / 脂質代謝 / 酸化ストレス / 腸内細菌叢
Outline of Research at the Start

本研究では、非アルコール性脂肪性肝炎を伴った高度肥満症に対して減量・代謝改善手術を行った患者の口腔内・腸内細菌叢の変化を確認し、同時に血液や手術中に非アルコール性脂肪性肝炎の診断のために採取した肝生検標本を用いて減量・代謝改善手術によって起こる生体内の代謝変化を詳細に確認しながら、肝線維化の進展・改善のメカニズムについて検討を行うものである。代謝変化は、ブドウ糖負荷試験、肝機能などの血液検査所見、マルチオミックス解析による網羅的なタンパク同定、細菌叢のメタゲノム解析、肝生検標本の線維化に関連するシグナル伝達因子に対する免疫組織染色などを併用して行い、統計学的解析を行い総合的に検討する。

Outline of Final Research Achievements

We aimed to clarify the mechanism of liver fibrosis due to metabolic dysfunction associated steatohepatitis in patients with severe obesity. Omics analyses revelaed that fatty acids related to arachidonic acid cascade and some proteins related to TGF-β signal had a significant correlations with liver fibrosis. In addtion, gut and microbiota recovered their diversities after metabolic and bariatric surgery, moreover, recovery of the diversity led to good weight-loss and metabolic effects compared to the non-recovery group. Our results suggests that organs and microbiota makes an complex axis in our body, and we will aimt to clarify this axix in the next studies.

Academic Significance and Societal Importance of the Research Achievements

外科治療としては減量・代謝改善手術は、国外での術式や手術症例数には及ばないのが国内の現状である。一方で、高度肥満症やこれに関連する疾患に対する基礎や臨床研究の多くは内科的な分野から発信されるものであるため外科治療を関連された報告は国際的にもきわめて少ない。この点から、本研究では多くの英語論文を含めた研究成果を発信出来ており、今後減量・代謝改善手術の治療効果を多方面から研究し多くの分野と共同研究を行うことは科学的にも非常に意義があるものと考えている。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (19 results)

All 2024 2023 2022

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Effects of laparoscopic sleeve gastrectomy on nonalcoholic fatty liver disease and TGF-β signaling pathway2024

    • Author(s)
      Kumagai H, Sasaki A, Umemura A, Kakisaka K, Iwaya T, Nishizuka SS.
    • Journal Title

      Endocrine Journal

      Volume: 71 Issue: 2 Pages: 139-152

    • DOI

      10.1507/endocrj.EJ23-0411

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictive factors involving the remission and recurrence of hypertension post-laparoscopic sleeve gastrectomy in Japanese patients with severe obesity2024

    • Author(s)
      Kumagai Hideki、Sasaki Akira、Umemura Akira、Tanahashi Yota、Iwasaki Takafumi、Ando Taro、Katagiri Hirokatsu、Nitta Hiroyuki
    • Journal Title

      PLOS ONE

      Volume: 19 Issue: 12 Pages: e0314792-e0314792

    • DOI

      10.1371/journal.pone.0314792

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Relationships Between Changes in Serum Ketone Body Levels and Metabolic Effects in Patients with Severe Obesity Who Underwent Laparoscopic Sleeve Gastrectomy2024

    • Author(s)
      Umemura Akira、Sasaki Akira、Kumagai Hideki、Tanahashi Yota、Iwasaki Takafumi、Nitta Hiroyuki
    • Journal Title

      Obesity Surgery

      Volume: 34 Issue: 7 Pages: 2607-2616

    • DOI

      10.1007/s11695-024-07337-8

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gastric cancer after laparoscopic adjustable gastric banding: A case report2024

    • Author(s)
      Kanno Masaki、Umemura Akira、Baba Shigeaki、Nikai Haruka、Sugimoto Ryo、Sasaki Akira
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 119 Pages: 109714-109714

    • DOI

      10.1016/j.ijscr.2024.109714

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship between the changes in hepatokine levels and metabolic effects after laparoscopic sleeve gastrectomy in severely obese patients2023

    • Author(s)
      Umemura Akira、Sasaki Akira、Takamura Toshinari、Takayama Hiroaki、Takeshita Yumie、Toya Yosuke、Kakisaka Keisuke、Hasegawa Yutaka、Ishigaki Yasushi
    • Journal Title

      Surgery Today

      Volume: 未定 Issue: 6 Pages: 581-590

    • DOI

      10.1007/s00595-023-02767-w

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a Fatty Acid for Diagnosing Non-Alcoholic Steatohepatitis in Patients with Severe Obesity Undergoing Metabolic Surgery.2022

    • Author(s)
      Takahashi N, Sasaki A, Umemura A, Sugai T, Kakisaka K, Ishigaki Y.
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 11 Pages: 2920-2920

    • DOI

      10.3390/biomedicines10112920

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 他疾患の手術を控えた高度肥満症患者に対するメタボリックサージェリーの意義2024

    • Author(s)
      梅邑 晃
    • Organizer
      第79回日本消化器外科学会総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 減量・代謝改善手術の現況と未来 減量・代謝改善手術による閉塞型睡眠時無呼吸と高血圧の改善効果の関連2024

    • Author(s)
      梅邑 晃
    • Organizer
      第49回日本外科系連合学会 2024年
    • Related Report
      2024 Annual Research Report
  • [Presentation] NASHの病態解明に基づく診療戦略 NASH合併高度肥満症患者に対する減量・代謝改善手術によるNASHの病理組織学的改善効果とオミックス解析の結果から見た今後の展望2024

    • Author(s)
      梅邑 晃
    • Organizer
      第110回日本消化器病学会総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Changes in left ventricular parameters after laparoscopic sleeve gastrectomy in patients with severe obesity2024

    • Author(s)
      Umemura A
    • Organizer
      IFSO 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Volumetric parameters are useful for evaluating weight-loss and metabolic effects after bariatric and metabolic surgery2024

    • Author(s)
      Umemura A
    • Organizer
      ELSA 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Will preoperative GERD change the choice of the bariatric and metabolic procedures?2024

    • Author(s)
      Umemura A
    • Organizer
      TEAMS meeting 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 非アルコール性脂肪性肝炎合併高度肥満症患者の減量・代謝改善手術前後の血中ケトン体と治療効果の関連2024

    • Author(s)
      梅邑 晃
    • Organizer
      日本臨床栄養代謝学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 高頻度栄養指導が減量・代謝改善手術患者に対する体重減少に及ぼす影響2024

    • Author(s)
      梅邑 晃
    • Organizer
      日本外科学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 腹腔鏡下スリーブ状胃切除術術後の縦隔脂肪量の変化と呼吸機能の関連2024

    • Author(s)
      棚橋 洋太
    • Organizer
      日本外科学会
    • Related Report
      2023 Research-status Report
  • [Presentation] MASH合併高度肥満症患者に対する減量・代謝改善手術によるMASHの病理組織学的改善効果とオミックス解析の結果から見た今後の展望2024

    • Author(s)
      梅邑 晃
    • Organizer
      日本消化器病学会
    • Related Report
      2023 Research-status Report
  • [Presentation] Will preoperative GERD change the choice of the bariatric and metabolic procedures?2024

    • Author(s)
      Umemura A
    • Organizer
      TEAMS meeting
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 減量・代謝改善手術が脂肪酸代謝に与える影響2022

    • Author(s)
      高橋 眞人、梅邑 晃、棚橋 洋太、熊谷 秀基、二階 春香、片桐 弘勝、 鈴木 信、秋山 有史、新田 浩幸、佐々木 章
    • Organizer
      日本肥満症治療学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Dynamic changes of the 5Gs by metabolic surgery and the 5Gs’ important role for improving comorbidities2022

    • Author(s)
      Umemura A
    • Organizer
      The 5Gs on Obesity and Diabetes Research; GLP-1, GIP, Glucagon, Ghrelin and Gut hormones
    • Related Report
      2022 Research-status Report
    • Invited

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Published: 2022-04-19   Modified: 2026-01-16  

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