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A novel prophylaxis for gut GVHD through mirobiota analysis

Research Project

Project/Area Number 19K17828
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto University

Principal Investigator

Arai Yasuyuki  京都大学, 医学研究科, 助教 (10826564)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腸内細菌叢 / 腸管細菌叢 / 移植片対宿主病 / 骨髄移植
Outline of Research at the Start

同種造血幹細胞移植は、造血器腫瘍の根治的治療であるが、移植後には様々な合併症が知られる。特に重篤な合併症である腸管の急性移植片対宿主病(GVHD)に関しては、発症予知バイオマーカーや、局所的予防・治療法が探索されてきたが、未だ確立されたものはない。
近年、炎症性腸疾患など腸管の免疫疾患において、腸内細菌叢の構成変化(dysbiosis)と病態との関連が証明されてきた。この知見から推察すると、患者腸管粘膜に対するドナーリンパ球の攻撃(同種免疫)である腸管GVHDにおいても、dysbiosisが関連する可能性がある。

Outline of Final Research Achievements

This study can be divided into (1) collection and identification of intestinal microbiota after bone marrow transplantation for hematopoietic tumors, (2) classification of intestinal microbiota by machine learning using AI, and integration and analysis with post-transplant clinical database, (3) similar investigation in mouse experimental models and prevention experiments using live bacteria preparations, and preparation for human clinical trials based on these studies. The first is the collection of intestinal microbiota.
The collection of intestinal microbiota in (1) will be conducted weekly for 2 months from the start of the pre-transplantation treatment.
The patient's stool samples will be collected weekly for 2 months from the start of the pre-transplantation treatment. The nucleotide sequence of the 16S ribosomal RNA-coding gene, which is a gene specific to the bacteria, will be determined using a next-generation sequencer.

Academic Significance and Societal Importance of the Research Achievements

検体採取は順調に進行し、これまでに合計21患者を対象とし、100サンプル以上を検討した。予定したプロトコールによって、患者からの同意取得、検体の採取、院内検査室への搬送、解析研究室への輸送、検体の保存、次世代シーケンスを用いた測定、コンピュータを用いた解析には大きな問題は発生せず、予定通り進捗している。結果は、属レベルまでの細菌分類が可能であった。

Report

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

    (18 results)

All 2022 2021 2020 2019

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Allogeneic hematopoietic stem cell transplantation for adult Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia in second complete remission2022

    • Author(s)
      Kaito Satoshi、Arai Yasuyuki、Kako Shinichi
    • Journal Title

      Transplantation and Cellular Therapy

      Volume: 0 Issue: 6 Pages: 0-0

    • DOI

      10.1016/j.jtct.2022.03.017

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coexistence of HLA and KIR ligand mismatches as a risk factor for viral infection early after cord blood transplantation2022

    • Author(s)
      Iemura Tomoki、Arai Yasuyuki、Takaori-Kondo Akifumi、the Kyoto Stem Cell Transplantation Group (KSCTG)
    • Journal Title

      Bone Marrow Transplantation

      Volume: 0 Issue: 5 Pages: 0-0

    • DOI

      10.1038/s41409-022-01621-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of indices for predicting recovery of exercise tolerance in patients surviving allogenic hematopoietic stem cell transplantation2022

    • Author(s)
      Hamada Ryota、Kondo Tadakazu、Harada Kazuhiro、Murao Masanobu、Miyasaka Junsuke、Yoshida Michiko、Yonezawa Honami、Nankaku Manabu、Arai Yasuyuki、Kanda Junya、Takaori-Kondo Akifumi、Ikeguchi Ryosuke、Matsuda Shuichi
    • Journal Title

      Supportive Care in Cancer

      Volume: 30 Issue: 5 Pages: 4027-4034

    • DOI

      10.1007/s00520-022-06822-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a quantitative prediction model for peripheral blood stem cell collection yield in the plerixafor era2022

    • Author(s)
      Ishii Akira、Jo Tomoyasu、Arai Yasuyuki、Oshima Shinichiro、Kanda Junya、Kitawaki Toshio、Matsui Keiko、Niwa Norimi、Nakagawa Yoko、Takaori-Kondo Akifumi、Nagao Miki
    • Journal Title

      Cytotherapy

      Volume: 24 Issue: 1 Pages: 49-58

    • DOI

      10.1016/j.jcyt.2021.09.004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy‐refractory or relapsed disease prior to allogeneic stem cell transplantation2021

    • Author(s)
      Nakamura Momoko、Arai Yasuyuki、Hirabayashi Shigeki、Kondo Tadakazu、Doki Noriko、Uchida Naoyuki、Fukuda Takahiro、Ozawa Yukiyasu、Tanaka Masatsugu、Sawa Masashi、Katayama Yuta、Kanda Yoshinobu、Shiratori Souichi、Nakamae Hirohisa、Yoshioka Satoshi、Onizuka Makoto、Ichinohe Tatsuo、Atsuta Yoshiko、Kako Shinichi
    • Journal Title

      British Journal of Haematology

      Volume: 194 Issue: 2 Pages: 403-413

    • DOI

      10.1111/bjh.17646

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Higher exercise tolerance early after allogeneic hematopoietic stem cell transplantation is the predictive marker for higher probability of later social reintegration2021

    • Author(s)
      Hamada Ryota、Arai Yasuyuki、Kondo Tadakazu、Harada Kazuhiro、Murao Masanobu、Miyasaka Junsuke、Yoshida Michiko、Yonezawa Honami、Nankaku Manabu、Ouchi Sayako、Kitakubo Wakako、Wadayama Tomoko、Kanda Junya、Takaori-Kondo Akifumi、Ikeguchi Ryosuke、Matsuda Shuichi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-86744-8

    • NAID

      120007026448

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation2021

    • Author(s)
      Onda Yoshiyuki、Kanda Junya、Hanaoka Nozomu、Watanabe Mizuki、Arai Yasuyuki、Hishizawa Masakatsu、Kondo Tadakazu、Yamashita Kouhei、Nagao Miki、Fujimoto Tsuguto、Takaori-Kondo Akifumi
    • Journal Title

      Annals of Hematology

      Volume: 100 Issue: 3 Pages: 753-761

    • DOI

      10.1007/s00277-021-04414-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Minimal residual disease (MRD) positivity at allogeneic hematopoietic cell transplantation, not the quantity of MRD, is a risk factor for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia2021

    • Author(s)
      Akahoshi Yu、Arai Yasuyuki、Nishiwaki Satoshi、Mizuta Shuichi、Marumo Atsushi、Uchida Naoyuki、Kanda Yoshinobu、Sakai Hitoshi、Takada Satoru、Fukuda Takahiro、Fujisawa Shin、Ashida Takashi、Tanaka Junji、Atsuta Yoshiko、Kako Shinichi
    • Journal Title

      International Journal of Hematology

      Volume: - Issue: 6 Pages: 832-839

    • DOI

      10.1007/s12185-021-03094-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia conducted in Japan during the past quarter century2020

    • Author(s)
      Yanada Masamitsu、Takami Akiyoshi、Yamasaki Satoshi、Arai Yasuyuki、Konuma Takaaki、Uchida Naoyuki、Najima Yuho、Fukuda Takahiro、Tanaka Masatsugu、Ozawa Yukiyasu、Ikegame Kazuhiro、Takanashi Minoko、Ichinohe Tatsuo、Okamoto Shinichiro、Atsuta Yoshiko、Yano Shingo
    • Journal Title

      Annals of Hematology

      Volume: 99 Issue: 6 Pages: 1351-1360

    • DOI

      10.1007/s00277-020-04051-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group2020

    • Author(s)
      Watanabe Mizuki、Kanda Junya、Arai Yasuyuki、Takaori-Kondo Akifumi、et al
    • Journal Title

      Biology of Blood and Marrow Transplantation

      Volume: 26 Issue: 12 Pages: 2346-2358

    • DOI

      10.1016/j.bbmt.2020.07.032

    • Related Report
      2020 Research-status Report
  • [Journal Article] Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation2020

    • Author(s)
      Noguchi Misa、Chen-Yoshikawa Toyofumi F.、Arai Yasuyuki、Kondo Tadakazu、Ohsumi Akihiro、Nakajima Daisuke、Hamaji Masatsugu、Takita Junko、Takaori-Kondo Akifumi、Date Hiroshi
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: - Issue: 4 Pages: 1549-1557.e4

    • DOI

      10.1016/j.jtcvs.2020.10.065

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drug monitoring for mycophenolic acid in graft‐ vs ‐host disease prophylaxis in cord blood transplantation2020

    • Author(s)
      Muranushi Hiroyuki、Kanda Junya、Arai Yasuyuki、Shindo Takero、Hishizawa Masakatsu、Yamamoto Takashi、Kondo Tadakazu、Yamashita Kohei、Matsubara Kazuo、Takaori‐Kondo Akifumi
    • Journal Title

      British Journal of Clinical Pharmacology

      Volume: 86 Issue: 12 Pages: 2464-2472

    • DOI

      10.1111/bcp.14354

    • NAID

      120006938957

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indication and benefit of upfront hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma in the era of ALL-type induction therapies2020

    • Author(s)
      Morita-Fujita Mari、Kyoto Stem Cell Transplantation Group (KSCTG)、Arai Yasuyuki、Yoshioka Satoshi、Ishikawa Takayuki、Kanda Junya、Kondo Tadakazu、Akasaka Takashi、Ueda Yasunori、Imada Kazunori、Moriguchi Toshinori、Yago Kazuhiro、Kitano Toshiyuki、Yonezawa Akihito、Nohgawa Masaharu、Takaori-Kondo Akifumi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-78334-x

    • NAID

      120006956388

    • Related Report
      2020 Research-status Report
  • [Journal Article] Activation of interferon regulatory factor 7 in plasmacytoid dendritic cells promotes experimental autoimmune pancreatitis2020

    • Author(s)
      Minaga K, Watanabe T, Arai Y, Shiokawa M, Hara A, Yoshikawa T, Kamata K, Yamashita K, Kudo M
    • Journal Title

      J Gastroenterol

      Volume: - Issue: 5 Pages: 565-576

    • DOI

      10.1007/s00535-020-01662-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors and appropriate therapeutic strategies for thrombotic microangiopathy after allogeneic HSCT2020

    • Author(s)
      Matsui Hiroyuki、Arai Yasuyuki、et al
    • Journal Title

      Blood Advances

      Volume: 4 Issue: 13 Pages: 3169-3179

    • DOI

      10.1182/bloodadvances.2020002007

    • NAID

      120006875283

    • Related Report
      2020 Research-status Report
  • [Journal Article] Impact of HLA class I allele-level mismatch on viral infection within 100?days after cord blood transplantation2020

    • Author(s)
      Iemura Tomoki、Arai Yasuyuki、Kanda Junya、Kitawaki Toshio、Hishizawa Masakatsu、Kondo Tadakazu、Yamashita Kouhei、Takaori-Kondo Akifumi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-78259-5

    • Related Report
      2020 Research-status Report
  • [Presentation] Dysbiosis in gut microbiota after allogeneic hematopoietic stem cell transplantation can be determined by the combination of conditioning regimen and antibiotic usage2019

    • Author(s)
      Yasuyuki Arai, Takamitsu Tsukahara, Miki Nagao, Tadakazu Kondo, Akifumi Takaori-Kondo
    • Organizer
      24th European Hematology Association (Amsterdam, Netherland)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 同種移植後の腸内細菌叢の変化に対する前処置および抗生剤使用の影響2019

    • Author(s)
      新井康之, 塚原 隆充, 松元 加奈, 長尾 美紀, 近藤 忠一, 髙折 晃史
    • Organizer
      第81回日本血液学会総会(東京)
    • Related Report
      2019 Research-status Report

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

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