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Elucidation of liver disease formation by bacterial species analysis detected in human portal blood

Research Project

Project/Area Number 19K08451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Watanabe Tsunamasa  聖マリアンナ医科大学, 医学部, 准教授 (20338528)

Project Period (FY) 2019-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腸内細菌叢 / 肝疾患 / 門脈血 / 腸内細菌 / 門脈 / 門脈血液 / 次世代シークエンス
Outline of Research at the Start

腸内環境からみた新たな肝疾患治療戦略立案の科学的根拠を見出すことを目的とし、これまでに食道胃静脈瘤治療時に血管カテーテルから無菌的に採取した門脈血液内に細菌DNAが存在することを確認してきた。
本研究では独自の方法で採取したヒト門脈血液を用いて、これまでの成果を飛躍的に発展させることを目的に門脈内に侵入する腸内細菌のメタゲノム解析を行い、同時に門脈血中の細菌由来代謝産物のメタボローム解析により肝病態に影響を与える生理活性因子を同定し、腸内細菌叢、門脈血中の細菌、門脈血中の生理活性物質、肝病態の形成ならびに進展との関係を明らかにする。

Outline of Final Research Achievements

To find a scientific basis for a new treatment strategy for liver disease from the viewpoint of the intestinal environment, a total of 28 cases of human portal vein blood were collected by a unique method. Furthermore, we performed intestinal flora metagenomic analysis by next-generation sequencing, including feces and portal vein blood collected from the same individual at the same time. The results revealed that bacterial DNA was detected in the portal blood flow in about half of the cases, and that the bacterial flora detected in the portal blood and feces in the same case was not the equal. Even for the same liver disease, the bacterial species detected in the portal vein blood differed from each case, and a consistent tendency could not be obtained and a clear association with the disease could not be found.

Academic Significance and Societal Importance of the Research Achievements

近年、増加傾向にあるアルコール性肝疾患や非アルコール性脂肪性肝炎において、肝病態進展と腸内細菌叢の関連が指摘されているが、ヒトにおいて腸管粘膜を通過し門脈を通って肝臓に流入する細菌について検討した報告は少なく、今回独自の方法により採取した門脈血を用いて腸内細菌叢メタゲノム解析を試みた。肝疾患患者の約半数で閉鎖系の門脈血流に細菌が流入している可能性を見出したが、個体差が大きいことも明らかとなった。今後は、肝疾患患者の腸内細菌叢の改変による治療介入の可能性について、さらなる検討が必要と考えられた。

Report

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

    (20 results)

All 2022 2021 2020 2019

All Journal Article (20 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 20 results,  Open Access: 9 results)

  • [Journal Article] Mac‐2‐binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C2022

    • Author(s)
      Kawata Kazuhito、Watanabe Tsunamasa、Tsubota Akihito
    • Journal Title

      Hepatology Communications

      Volume: - Issue: 8 Pages: 1-15

    • DOI

      10.1002/hep4.1941

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B2022

    • Author(s)
      Nagura Yoshihito、Matsuura Kentaro、Iio Etsuko、Fujita Koji、Inoue Takako、Matsumoto Akihiro、Tanaka Eiji、Nishiguchi Shuhei、Kang Jong-Hon、Matsui Takeshi、Enomoto Masaru、Ikeda Hiroki、Watanabe Tsunamasa、Okuse Chiaki、Tsuge Masataka、Atsukawa Masanori、Tateyama Masakuni、Kataoka Hiromi、Tanaka Yasuhito
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 2 Pages: e0263844-e0263844

    • DOI

      10.1371/journal.pone.0263844

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time‐course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis2021

    • Author(s)
      Atsukawa Masanori、Watanabe Tsunamasa、Iwakiri Katsuhiko
    • Journal Title

      Hepatology Research

      Volume: 52 Issue: 3 Pages: 235-246

    • DOI

      10.1111/hepr.13739

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: A multicenter analysis2021

    • Author(s)
      Chuma Makoto、Hattori Nobuhiro、Watanabe Tsunamasa、Maeda Shin
    • Journal Title

      Hepatology Research

      Volume: 52 Issue: 3 Pages: 269-280

    • DOI

      10.1111/hepr.13732

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study2021

    • Author(s)
      Suzuki Fumitaka、Watanabe Tsunamasa、Kumada Hiromitsu
    • Journal Title

      BMC Gastroenterology

      Volume: 21 Issue: 1

    • DOI

      10.1186/s12876-021-02008-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of esophagogastric varices associated with oxaliplatin administration2021

    • Author(s)
      Satta Yosuke、Shigefuku Ryuta、Watanabe Tsunamasa、Mizukami Takuro、Tsuda Takashi、Suzuki Tatsuya、Ehira Takuya、Hattori Nobuhiro、Kiyokawa Hirofumi、Nakahara Kazunari、Ikeda Hiroki、Matsunaga Kotaro、Takahashi Hideaki、Matsumoto Nobuyuki、Okuse Chiaki、Suzuki Michihiro、Sunakawa Yu、Yasuda Hiroshi、Itoh Fumio
    • Journal Title

      JGH Open

      Volume: 5 Issue: 11 Pages: 1289-1297

    • DOI

      10.1002/jgh3.12668

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics and Prognosis of De Novo Hepatocellular Carcinoma After Sustained Virologic Response2021

    • Author(s)
      Toyoda Hidenori、Watanabe Tsunamasa、Tanaka Junko
    • Journal Title

      Hepatology Communications

      Volume: 5 Issue: 7 Pages: 1290-1299

    • DOI

      10.1002/hep4.1716

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir2021

    • Author(s)
      Nguyen Mindie H.、Watanabe Tsunamasa、Enomoto Masaru
    • Journal Title

      American Journal of Gastroenterology

      Volume: 116 Issue: 6 Pages: 1264-1273

    • DOI

      10.14309/ajg.0000000000001157

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment and Renal Outcomes Up to 96 Weeks After Tenofovir Alafenamide Switch From Tenofovir Disoproxil Fumarate in Routine Practice2021

    • Author(s)
      Toyoda Hidenori、Watanabe Tsunamasa、Nguyen Mindie H.
    • Journal Title

      Hepatology

      Volume: 74 Issue: 2 Pages: 656-666

    • DOI

      10.1002/hep.31793

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients2021

    • Author(s)
      Urata Noboru、Watanabe Tsunamasa、Hirashima Noboru、Yokomaku Yoshiyuki、Imamura Junji、Iwatani Yasumasa、Shimada Masaaki、Tanaka Yasuhito
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 4 Pages: 833-833

    • DOI

      10.3390/jcm10040833

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and Efficacy of Lenvatinib Treatment in Child-Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis2020

    • Author(s)
      Ogushi Katsuaki、Chuma Makoto、Uojima Haruki、Hidaka Hisashi、Numata Kazushi、Kobayashi Satoshi、Hirose Shunji、Hattori Nobuhiro、Fujikawa Tomoaki、Nakazawa Takahide、Wada Naohisa、Iwasaki Shuichiro、Fukushima Taito、Sano Yusuke、Ueno Makoto、Kawano Kuniyuki、Tsuruya Kota、Shomura Masako、Watanabe Tsunamasa, et al.
    • Journal Title

      Clinical and Experimental Gastroenterology

      Volume: Volume 13 Pages: 385-396

    • DOI

      10.2147/ceg.s256691

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study2020

    • Author(s)
      Atsukawa Masanori、Tsubota Akihito、Kondo Chisa、Toyoda Hidenori、Nakamuta Makoto、Takaguchi Koichi、Watanabe Tsunamasa、et al.
    • Journal Title

      Infectious Diseases and Therapy

      Volume: 9 Issue: 4 Pages: 851-866

    • DOI

      10.1007/s40121-020-00329-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study2020

    • Author(s)
      Nozaki, A. Atsukawa, M. Ogawa, S. Itokawa, N. Arai, T. Ikegami, T. Tsubota, A. Genda, T. Okubo, H. Mikami, S. Morishita, A. Moriya, A. Tani, J. Tachi, Y. Hotta, N. Ishikawa, T. Okanoue, T. Tanaka, Y. Kumada, T. Iwakiri, K. Maeda, S. K. T. K. Liver Study Group
    • Journal Title

      Hepatol Int

      Volume: - Issue: 2 Pages: 225-238

    • DOI

      10.1007/s12072-020-10019-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Marked heterogeneity in the diagnosis of compensated cirrhosis of patients with chronic hepatitis C virus infection in a real-world setting: A large, multicenter study from Japan2020

    • Author(s)
      Toyoda H, Atsukawa M, Watanabe T..., Tsubota A, et al
    • Journal Title

      J Gastroenterol Hepatol

      Volume: - Issue: 8 Pages: 1420-1425

    • DOI

      10.1111/jgh.14982

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema2020

    • Author(s)
      Atsukawa M, Tsubota A, Takaguchi K, Toyoda H, Iwasa M, Ikegami T, Chuma M, Nozaki A, Uojima H, Hiraoka A, Fukunishi S, Yokohama K, Tada T, Kato K, Abe H, Tani J, Okubo H, Watanabe T, et al.
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: - Issue: 7 Pages: 1229-1237

    • DOI

      10.1111/jgh.14965

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of ombitasvir/paritaprevir/ritonavir and ribavirin for chronic hepatitis patients infected with genotype 2a in Japan.2019

    • Author(s)
      Atsukawa M, Tsubota A, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, Tada T, Tsutsui A, Ikeda H, Abe H, Kato K, Uojima H, Ikegami T, Asano T, Kondo C, Koeda M, Okubo T, Arai T, Iwashita-Nakagawa A, Itokawa N, Kumada T, Iwakiri K
    • Journal Title

      Hepatol Res

      Volume: 49 Issue: 4 Pages: 369-376

    • DOI

      10.1111/hepr.13292

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study.2019

    • Author(s)
      Atsukawa M, Tsubota A, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, Michitaka K, Ikegami T, Nozaki A, Uojima H, Fukunishi S, Genda T, Abe H, Hotta N, Tsuji K, Ogawa C, Tachi Y, Shima T, Shimada N, Kondo C, Akahane T, Aizawa Y, Tanaka Y, Kumada T, Iwakiri K
    • Journal Title

      Aliment Pharmacol Ther

      Volume: 49 Issue: 9 Pages: 1230-1241

    • DOI

      10.1111/apt.15218

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trends and Efficacy of Interferon-Free Anti-hepatitis C Virus Therapy in the Region of High Prevalence of Elderly Patients, Cirrhosis, and Hepatocellular Carcinoma: A Real-World, Nationwide, Multicenter Study of 10 688 Patients in Japan2019

    • Author(s)
      Toyoda H, Atsukawa M, Uojima H, Nozaki A, Tamai H, Takaguchi K, Fujioka S, Nakamuta M, Tada T, Yasuda S, Chuma M, Senoh T, Tsutsui A, Yamashita N, Hiraoka A, Michitaka K, Shima T, Akahane T, Itobayashi E, Watanabe T, et al.
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 6 Issue: 5

    • DOI

      10.1093/ofid/ofz185

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of 8‐week glecaprevir/pibrentasvir treatment in direct‐acting antiviral‐naive noncirrhotic HCV genotype 1 and 2 infected patients in a real‐world setting in Japan2019

    • Author(s)
      Ikeda H, Watanabe T, Iio E, Tsubota A, Hiraoka A, Nozaki A, Okubo H, Tachi Y, Moriya A, Oikawa T, Matsumoto Y, Tsuruoka S, Tani J, Kikuchi K, Iwakiri K, Tanaka Y, Kumada T, et al.
    • Journal Title

      Journal of Viral Hepatitis

      Volume: 26 Issue: 11 Pages: 1266-1275

    • DOI

      10.1111/jvh.13170

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Real‐world experience of 12‐week direct‐acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection2019

    • Author(s)
      Toyoda H, Atsukawa M, Watanabe T, et al
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: - Issue: 5 Pages: 855-861

    • DOI

      10.1111/jgh.14874

    • Related Report
      2019 Research-status Report
    • Peer Reviewed

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Published: 2019-04-18   Modified: 2023-01-30  

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