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Screening for gut microbiota-derived metabolites that stimulate intestinal stem cells

Research Project

Project/Area Number 16K15422
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

Fujishiro Mitsuhiro  東京大学, 医学部附属病院, 准教授 (70396745)

Co-Investigator(Kenkyū-buntansha) 池田 祐一  東京大学, 医学部附属病院, 特任准教授 (10744419)
熊谷 英敏  東京大学, 医学部附属病院, 特任助教 (20281008)
山下 裕玄  東京大学, 医学部附属病院, 講師 (50599397)
森田 啓行  東京大学, 医学部附属病院, 講師 (60323573)
浅岡 良成  東京大学, 医学部附属病院, 助教 (90431858)
Project Period (FY) 2016-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
KeywordsWntシグナル / 腸管幹細胞 / 常在性腸内細菌叢 / 生理活性代謝産物 / 内科 / 消化器内科 / 下部消化管 / 再生医学 / 生理活性
Outline of Final Research Achievements

This study is being conducted to identify gut microbiota-derived metabolites that stimulate intestinal stem cells. Utilizing a novel assay system targeting R-spondin-LGR4/5/6-ZNRF3/RNF43 axis, we first screened a small-molecule compound library and identified 2 unique compounds that enhance R-spondin activities. This proof-of-concept experiment suggests that this newly established assay is well suited for biochemical purification of bioactive metabolites from crude microbiota-derived extracts. We also conducted comprehensive metabolomic analysis and identified 54 metabolites from fecal extracts of germ-free mice that had received fecal microbiota transplantation (FMT). The biological activities of these metabolites are currently being examined.

Report

(2 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (34 results)

All 2017 2016

All Journal Article (34 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 34 results,  Open Access: 20 results,  Acknowledgement Compliant: 6 results)

  • [Journal Article] Periodontitis and myocardial hypertrophy2017

    • Author(s)
      Suzuki J, Sato H, Kaneko M, Yoshida A, Aoyama N, Akimoto S, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, IzumiY, Isobe M, Komuro I
    • Journal Title

      Hypertens Res

      Volume: [Epub ahead of print] Issue: 4 Pages: 324-328

    • DOI

      10.1038/hr.2016.146

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Guidelines for endoscopic managements of non-variceal upper gastrointestinal bleeding.2016

    • Author(s)
      Fujishiro M, Iguchi M, Kakushima N, Kato M, Sakata Y, Hoteya S, Kataoka M, Shimaoka S, Yahagi N, Fujimoto K.
    • Journal Title

      Dig Endosc.

      Volume: 28 Issue: 4 Pages: 363-378

    • DOI

      10.1111/den.12639

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Re-bleeding After Endoscopic Hemostasis for Peptic Ulcer Bleeding: Is eNough SAID or Are Other Factors Important?2016

    • Author(s)
      Fujishiro M, Ikeda Y.
    • Journal Title

      Dig Dis Sci.

      Volume: 61 Issue: 6 Pages: 1424-1425

    • DOI

      10.1007/s10620-016-4098-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful closure of a large perforation during colorectal endoscopic submucosal dissection by application of polyglycolic acid sheets and fibrin glue.2016

    • Author(s)
      Sakaguchi Y, Tsuji Y, Yamamichi N, Fujishiro M, Koike K.
    • Journal Title

      Gastrointest Endos.

      Volume: 84 Issue: 2 Pages: 374-375

    • DOI

      10.1016/j.gie.2016.03.787

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Registration Committee for Esophageal Cancer of the Japan Esophageal Society. Comprehensive Registry of Esophageal Cancer in Japan, 2009.2016

    • Author(s)
      Tachimori Y, Ozawa S, Numasaki H, Fujishiro M, Matsubara H, Oyama T, Shinoda M, Toh Y, Udagawa H, Uno T
    • Journal Title

      Esophagus.

      Volume: 13 Issue: 2 Pages: 110-137

    • DOI

      10.1007/s10388-016-0531-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor Content Chart-Assisted HER2/CEP17 Digital PCR Analysis of Gastric Cancer Biopsy Specimens.2016

    • Author(s)
      Matsusaka K, Ishikawa S, Nakayama A, Ushiku T, Nishimoto A, Urabe M, Kaneko N, Kunita A, Kaneda A, Aburatani H, Fujishiro M, Seto Y, Fukayama M.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0154430-e0154430

    • DOI

      10.1371/journal.pone.0154430

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Triamcinolone Injection and Shielding with Polyglycolic Acid Sheets and Fibrin Glue for Postoperative Stricture Prevention after Esophageal Endoscopic Resection: A Pilot Study.2016

    • Author(s)
      Sakaguchi Y, Tsuji Y, Fujishiro M, Kataoka Y, Takeuchi C, Yakabi S, Saito I, Shichijo S, Minatsuki C, Asada-Hirayama I, Yamaguchi D, Niimi K, Ono S, Kodashima S, Yamamichi N, Koike K.
    • Journal Title

      Am J Gastroenterol.

      Volume: 111 Issue: 4 Pages: 581-583

    • DOI

      10.1038/ajg.2016.60

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV.2016

    • Author(s)
      Onoyama H, Kamiya M, Kuriki Y, Komatsu T, Abe H, Tsuji Y, Yagi K, Yamagata Y, Aikou S, Nishida M, Mori K, Yamashita H, Fujishiro M, Nomura S, Shimizu N, Fukayama M, Koike K, Urano Y, Seto Y
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 26399-26399

    • DOI

      10.1038/srep26399

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoscopic ultrasound-guided fine-needle aspiration skill acquisition of gastrointestinal submucosal tumor by trainee endoscopists: A pilot study2016

    • Author(s)
      Niimi K, Goto O, Kawakubo K, Nakai Y, Minatsuki C, Asada-Hirayama I, Mochizuki S, Ono S, Kodashima S, Yamamichi N, Isayama H, Fujishiro M, Koike K.
    • Journal Title

      Endosc Ultrasound.

      Volume: 5 Issue: 3 Pages: 157

    • DOI

      10.4103/2303-9027.183970

    • URL

      https://pure.teikyo.jp/en/publications/878ec838-ed70-4c55-a64a-94e30b041fb3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bleeding after endoscopic submucosal dissection: Risk factors and preventive methods2016

    • Author(s)
      Kataoka Y, Tsuji Y, Sakaguchi Y, Minatsuki C, Asada-Hirayama I, Niimi K, Ono S, Kodashima S, Yamamichi N, Fujishiro M, Koike K
    • Journal Title

      World J Gastroenterol.

      Volume: 22 Issue: 26 Pages: 5927

    • DOI

      10.3748/wjg.v22.i26.5927

    • URL

      https://pure.teikyo.jp/en/publications/63851f87-5221-4252-b3f3-0c9f3f37738d

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Congress report: Exchange of opinions in Tokyo, 2016 between Japan Gastroenterological Endoscopy Society (JGES) and counterparts from abroad.2016

    • Author(s)
      Fujishiro M, Yasuda I.
    • Journal Title

      Dig Endosc.

      Volume: 28 Issue: 6 Pages: 642-644

    • DOI

      10.1111/den.12703

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current Practices in the Management of Antithrombotic Therapy During the Periendoscopic Period for Patients With Cardiovascular Disease2016

    • Author(s)
      Ono S, Saito I, Ikeda Y, Fujishiro M, Komuro I, Koike K.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 5 Pages: 530-534

    • DOI

      10.1536/ihj.16-057

    • NAID

      130005266608

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Updated evidence on endoscopic resection of early gastric cancer from Japan.2016

    • Author(s)
      Fujishiro M, Yoshida S, Matsuda R, Narita A, Yamashita H, Seto Y.
    • Journal Title

      Gastric Cancer.

      Volume: 20 Issue: S1 Pages: 39-44

    • DOI

      10.1007/s10120-016-0647-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and Effectiveness of Endovenous Laser Ablation Combined With Ligation for Severe Saphenous Varicose Veins in Japanese Patients2016

    • Author(s)
      Izumi M, Ikeda Y, Yamashita H, Asaoka Y, Fujishiro M, Shin M, Abo Y.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 1 Pages: 87-90

    • DOI

      10.1536/ihj.15-282

    • NAID

      130005120984

    • ISSN
      1349-2365, 1349-3299
    • URL

      https://pure.teikyo.jp/en/publications/d84b0eb4-7d54-4d1f-991f-0186b7909879

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cacao polyphenols ameliorate autoimmune myocarditis in mice2016

    • Author(s)
      Zempo H, Suzuki J, Watanabe R, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 203-209

    • DOI

      10.1038/hr.2015.136

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure2016

    • Author(s)
      Watanabe R, Suzuki J, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 237-244

    • DOI

      10.1038/hr.2015.141

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice.2016

    • Author(s)
      Kobayashi N, Suzuki JI, Aoyama N, Sato H, Akimoto S, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Izumi Y, Isobe M.
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 10 Pages: 717-722

    • DOI

      10.1038/hr.2016.58

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Projections from single NUCB2/nesfatin-1 neuron in paraventricular nucleus to different brain regions involved in feeding2016

    • Author(s)
      Maejima Y, Kumamoto K, Takenoshita S, Shimomura K
    • Journal Title

      Brain Structure and Function

      Volume: in press Pages: 123-137

    • DOI

      10.1016/j.yjmcc.2016.03.017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Periodontitis May Deteriorate Sinus of Valsalva Dilatation in Marfan Syndrome Patients2016

    • Author(s)
      Suzuki J, Imai Y, Aoki M, Fujita D, Takeda N, Aoyama N, Wakayama K, Ikeda Y, Kumagai H, Akazawa H, Izumi Y, Isobe M, Komuro I, Hirata Y
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 4 Pages: 456-460

    • DOI

      10.1536/ihj.15-395

    • NAID

      130006895913

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Current therapies and investigational drugs for peripheral arterial disease2016

    • Author(s)
      Suzuki J, Shimamura M, Suda H, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Isobe M, Komuro I, Morishita R
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 183-191

    • DOI

      10.1038/hr.2015.134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Understanding vascular diseases: Lessons from premature aging syndromes2016

    • Author(s)
      Ikeda Y, Kumagai H, Motozawa Y, Suzuki J, Akazawa H, Komuro I
    • Journal Title

      Can J Cardiol

      Volume: 32 Issue: 5 Pages: 1-9

    • DOI

      10.1016/j.cjca.2015.12.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth Differentiation Factor 15 (GDF15) as a Reliable Biomarker for Cardiovascular Risk Assessment2016

    • Author(s)
      Ikeda Y1, Kumagai H, Motozawa Y, Suzuki J
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 1 Pages: 1-2

    • DOI

      10.1536/ihj.15-324

    • NAID

      130005120988

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early endoscopic management for early bowel obstruction after gastrectomy: a case report2016

    • Author(s)
      K. Higashizono, S. Aikou, K. Yagi, K. Mori, H. Yamashita, S. Nomura, Y. Seto
    • Journal Title

      Surg Case Rep

      Volume: 2 Issue: 1 Pages: 35-35

    • DOI

      10.1186/s40792-016-0164-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low density of CD204-positive M2 type tumor-associated macrophages in Epstein-Barr virus-associated gastric cancer: a clinicopathological study with digital image analysis.2016

    • Author(s)
      Ichimura T, Abe H, Morikawa T, Yamashita H, Ishikawa S, Ushiku T, Seto Y, Fukayama M.
    • Journal Title

      Hum Pathol.

      Volume: 56 Pages: 74-80

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radical esophagectomy for a 92-year-old woman with granulocyte colony-stimulating factor-producing esophageal squamous cell carcinoma: a case report.2016

    • Author(s)
      Kitani M, Yamagata Y, Tanabe A, Yagi K, Aikou S, Kiyokawa T, Nishida M, Yamashita H, Mori K, Nomura S, Seto Y.
    • Journal Title

      World J Surg Oncol.

      Volume: 14 Issue: 1 Pages: 264-264

    • DOI

      10.1186/s12957-016-1023-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Utility of Cystatin C for Estimating Glomerular Filtration Rate in Patients With Muscular Dystrophy2016

    • Author(s)
      Kimura K, Morita H, Daimon M, Horio M, Kawata T, Nakao T, Hirokawa M, Kitao R, Watanabe D, Komori T, Nagata T, Takeda S, Komaki H, Segawa K, Nakajima T, Takenaka K, Komuro I
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 3 Pages: 386-388

    • DOI

      10.1536/ihj.15-461

    • NAID

      130005153700

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fukutin gene mutations that cause left ventricular noncompaction2016

    • Author(s)
      Amiya E, Morita H, Hatano M, Nitta D, Hosoya Y, Maki H, Motozawa Y, Sato N, Ishiura H, Numakura S, Shintani Y, Kinugawa K, Takeda N, Shimizu J, Tsuji S, Komuro I.
    • Journal Title

      International Journal of Cardiology

      Volume: 222 Pages: 727

    • DOI

      10.1016/j.ijcard.2016.08.011

    • URL

      https://pure.teikyo.jp/en/publications/1c4cf5ad-9158-4757-b2fd-716521f62d9f

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart failure complicated by alveolar hemorrhage due to vascular collapse and amyloid deposits in wild-type transthyretin amyloidosis.2016

    • Author(s)
      Kido Y, Takahashi M, Fukuma N, Kawata T, Tanaka A, Hayashi A, Shibahara J, Daimon M, Morita H, Akazawa H, Komuro I.
    • Journal Title

      Cardiology

      Volume: 135 Issue: 4 Pages: 216-220

    • DOI

      10.1159/000446513

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Strategy for Heart Failure in Becker Muscular Dystrophy2016

    • Author(s)
      Kimura K, Morita H, Nakamura A, Takenaka K, Daimon M.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 5 Pages: 527-529

    • DOI

      10.1536/ihj.16-311

    • NAID

      130005266584

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Strategy for Genomic Research on Common Cardiovascular Diseases Aiming at the Realization of Precision Medicine: Personal Insights and Perspectives.2016

    • Author(s)
      Morita H, Komuro I.
    • Journal Title

      Circulation Research

      Volume: 119 Issue: 8 Pages: 900-903

    • DOI

      10.1161/circresaha.116.309802

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuromuscular Electrical Stimulation in Patients With Acute Myocardial Infarction2016

    • Author(s)
      Nakao T, Morita H.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 6 Pages: 659-660

    • DOI

      10.1536/ihj.16-498

    • NAID

      130005172026

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of oral treatment on physical function in older patients hospitalized for heart failure: A randomized clinical trial.2016

    • Author(s)
      Ueda K, Kasao M, Shimamura M, Haruta H, Nitta S, Kaneko M, Uemura Y, Morita H, Komuro I, Shirai T.
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 12 Pages: e0167933-e0167933

    • DOI

      10.1371/journal.pone.0167933

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The impact of direct-acting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma.2016

    • Author(s)
      Minami T, Tateishi R, Nakagomi R, Fujiwara N, Sato M, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Shiina S, Koike K
    • Journal Title

      J Hepatol.

      Volume: 65 Issue: 6 Pages: 1272-1273

    • DOI

      10.1016/j.jhep.2016.07.043

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion.2016

    • Author(s)
      Ikenoue T, Terakado Y, Nakagawa H, Hikiba Y, Fujii T, Matsubara D, Noguchi R, Zhu C, Yamamoto K, Kudo Y, Asaoka Y, Yamaguchi K, Ijichi H, Tateishi K, Fukushima N, Maeda S, Koike K, Furukawa Y
    • Journal Title

      Sci Rep

      Volume: 印刷中 Issue: 1 Pages: 23899-23899

    • DOI

      10.1038/srep23899

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2016-04-21   Modified: 2018-03-22  

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