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Prevention and treatment of inflammatory diseases: control of pharmacokinetics with probiotics

Research Project

Project/Area Number 15K08045
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionAomori University (2018-2019)
Keio University (2015-2017)

Principal Investigator

Mikiko Shimizu  青森大学, 薬学部, 教授 (90396391)

Co-Investigator(Kenkyū-buntansha) 橋口 正行  慶應義塾大学, 薬学部(芝共立), 准教授 (10271355)
Project Period (FY) 2015-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsプロバイオティクス / 炎症性腸疾患 / 間接リウマチ / サイトカイン / 薬物動態 / 細胞障害 / 副作用軽減 / メトトレキサート / 炎症性疾患 / 関節リウマチ / メトトレキセート / Methotrexate
Outline of Final Research Achievements

In experiments using human intestinal epithelial-like Caco-2 cells, we found that probiotics suppress intestinal inflammation and reduce the side effects of drug therapy.In experiments using human fibroblast-like synoviocytes-rheumatoid arthritis and collagen-induced arthritis rats, we found a bifidobacteria strain that exerts antirheumatic activity through suppression of signal transduction in inflammatory processes. In addition, it was confirmed that the effect was increased with the combined administration of the antirheumatic agent methotrexate.The results suggest that probiotics may change the pharmacokinetics of methotrexate.

Academic Significance and Societal Importance of the Research Achievements

病態モデルを用いた本研究の結果、プロバイオティクスは炎症性疾患(炎症性腸疾患および慢性関節リウマチ)の予防・治療効果を示すことが明らかとなった。特に、慢性関節リウマチ治療薬メトトレキセートとの併用において、治療効果の増大を示すと共に、薬物治療の副作用の軽減につながる可能性のある菌種を見出した。また、それらの作用機序についても明らかにした。従って、プロバイオティクス摂取は、炎症性疾患治療薬の適正使用、治療の効率化に寄与できると考えられる。

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017 2016 2015

All Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 10 results,  Acknowledgement Compliant: 7 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Factors contributing to the systemic clearance of infliximab with long-term administration in Japanese patients with Crohn’s disease: Analysis using population pharmacokinetics2020

    • Author(s)
      Matsuoka Katsuyoshi、Hamada Shunsuke、Shimizu Mikiko、Nanki Kosaku、Mizuno Shinta、Kiyohara Hiroki、Arai Mari、Sugimoto Shinya、Iwao Yasushi、Ogata Haruhiko、Hisamatsu Tadakazu、Nagauma Makoto、Kanai Takanori、Mochizuki Mayumi、Hashiguchi Masayuki
    • Journal Title

      Int. Journal of Clinical Pharmacology and Therapeutics

      Volume: 58 Issue: 02 Pages: 89-102

    • DOI

      10.5414/cp203569

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long‐term effect of NUDT15 R139C on hematologic indices in inflammatory bowel disease patients treated with thiopurine2019

    • Author(s)
      Akiyama Shintaro、Takenaka Kento、et al
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 34 Issue: 10 Pages: 1751-1757

    • DOI

      10.1111/jgh.14693

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparing torsemide versus furosemide in patients with heart failure: A meta-analysis.2019

    • Author(s)
      Kido K, Shimizu M, Hashiguchi M
    • Journal Title

      J. Am Pharm Assoc (2003)

      Volume: 59(3) Issue: 3 Pages: 432-438

    • DOI

      10.1016/j.japh.2019.01.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Factors Predicting the Therapeutic Response to Methotrexate in Japanese Patients with Rheumatoid Arthritis: A Hospital-Based Cohort Study2018

    • Author(s)
      Hakamata J, Kaneko Y, Shimizu M, Yamaoka K, Maruyama J, Takeuchi T, Mochizuki M, Hashiguchi M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 9 Pages: 1414-1422

    • DOI

      10.1248/bpb.b18-00247

    • NAID

      130007479889

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-09-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn’s disease.2018

    • Author(s)
      Matsuoka K, Hamada S, Shimizu M, Nanki K, Mizuno S, Kiyohara H, Arai M, Sugimoto S, Iwao Y, Ogata H, Hisamatsu T, Naganuma M, Kanai T, Mochizuki M, Hashiguchi M
    • Journal Title

      PLoS One

      Volume: 13(10) Pages: 1-10

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk factors for Hyperuricemia with HMG-CoA reductase inhibitors identified using a postmarketing surveillance database in Japan.2018

    • Author(s)
      Hashiguchi M, Hakamata J, Shimizu M, Maruyma J, Shiga T, Mochizuki M
    • Journal Title

      Jap J Clin Pharmacol Ther

      Volume: 49(4) Pages: 145-150

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors for rhabdomyolysis with HMG-CoA reductase inhibitors identified using a postmarketing surveillance database in Japan.2018

    • Author(s)
      Hashiguchi M, Hakamata J, Shimizu M, Maruyma J, Shiga T, Mochizuki M
    • Journal Title

      Int J Clin Pharmacol Ther

      Volume: 56(7) Issue: 07 Pages: 310-320

    • DOI

      10.5414/cp203237

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk Factor for Diabetes Mellitus and High Blood GlucoseWith HMG-CoA Reductase Inhibitors Using a Postmarketing Surveillance Database in Japan.2018

    • Author(s)
      Hashiguchi M, Maruyma J, Shimizu M, Takahashi D, Shiga T
    • Journal Title

      Clinical Pharmacology in Drug Development

      Volume: 7(8) Issue: 8 Pages: 800-810

    • DOI

      10.1002/cpdd.444

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors for abnormal hepatic enzyme elevation by methotrexate treatment in patients with rheumatoid arthritis: a hospital based-cohort study.2018

    • Author(s)
      Hakamata J, Hashiguchi M, Kaneko Y, Yamaoka K, Shimizu M, Maruyama J, Takeuchi T, Mochizuki M.
    • Journal Title

      Modern Rheumatology

      Volume: 2 Issue: 4 Pages: 1-10

    • DOI

      10.1080/14397595.2017.1414765

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ethnic and gender differences in genetic polymorphisms of tumor necrosis factor (TNF)-α in a Japanese population.2017

    • Author(s)
      Hakamata J, Hashiguchi M, Tsuru T, Tanaka T, Irie S, Shimizu M, Mochizuki M.
    • Journal Title

      Jpn J Clin Pharmacol Ther

      Volume: 48 Pages: 21-26

    • NAID

      130005606230

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ethnic and gender differences in genetic polymorphisms of tumor necrosis factor (TNF)-α in a Japanese population.2017

    • Author(s)
      Hakanmada J, Hashiguchi M, Thuru T, Tanaka T, Irie S, Shimizu M, Mochizuki M.
    • Journal Title

      Jpn J Clin Pharmacol Ther

      Volume: 48(2) Pages: 21-21

    • NAID

      130005606230

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response and pharmacokinetics in a Japanese population.2016

    • Author(s)
      Hashiguchi M, Shimizu M, Hakamata J, Tsuru T, Tanaka T, Suzaki M, Miyawaki K, Chiyoda T, Takeuchi O, Hiratsuka J, Irie S, Maruyama J, Mochizuki M.
    • Journal Title

      J Pharm Health Care Sci.

      Volume: 2 (35) Issue: 1

    • DOI

      10.1186/s40780-016-0069-0

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Preliminary study for predicting better methotrexate efficacy in Japanese patients with rheumatoid arthritis.2016

    • Author(s)
      Hashiguchi M, Tsuru T, Miyawaki K, Suzaki M, Hakamata J, Shimizu M, Irie S, Mochizuki M.
    • Journal Title

      J Pharm Health Care Sci

      Volume: 2(13) Issue: 1

    • DOI

      10.1186/s40780-016-0047-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sex Differences in mRNA Expression of Reduced Folate Carrier-1, Folypolyformyl Glutamate Synthase, And γ-Glutamyl Hydrolase in a Healthy Japanese Population.2016

    • Author(s)
      Hashiguchi M, Tanaka T, Shimizu M, Tsuru T, Chiyoda T, Miyawaki K, Irie S, Takeuchi O, Hakamata J, Mochizuki M.
    • Journal Title

      J Clin Pharmacol

      Volume: 56(12) Issue: 12 Pages: 1563-1569

    • DOI

      10.1002/jcph.760

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.2015

    • Author(s)
      Hashiguchi M, Imai S, Uehara K, Maruyama J, Shimizu M, Mochizuki M.
    • Journal Title

      PLoS One

      Volume: 10(12)e0144263 Issue: 12 Pages: e0144263-e0144263

    • DOI

      10.1371/journal.pone.0144263

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals.2015

    • Author(s)
      Shimizu M*, Hashiguchi M, Shiga T, Tamura HO, Mochizuki M.
    • Journal Title

      PLoS One

      Volume: 10(10)e0139795 Issue: 10 Pages: e0139795-e0139795

    • DOI

      10.1371/journal.pone.0139795

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia.2015

    • Author(s)
      Masayuki Hashiguchi, Yuriko Ohta, Mikiko Shimizu, Junya Maruyama and Mayumi Mochizuki*
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 1・14 Issue: 1

    • DOI

      10.1186/s40780-015-0014-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 日本人ループス腎炎患者におけるヒドロキシクロロキンの適正使用に関する検討2019

    • Author(s)
      清水美貴子、横川直人、杉井章二、瀬戸口京吾、大島美穂、古舘澄人、井沼道子、三浦裕也、橋口正行
    • Organizer
      第40回日本臨床薬理学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pharmacokinetics of hydroxychloroquine in systemic lupus erythematosus patients with renal impairment2019

    • Author(s)
      Yokogawa N、Hashiguchi M、Nagai Y、Shimada K、Sugii S、Ohshima M、Setoguchi K、Shimizu M
    • Organizer
      ACR 2019 (American College of Rheumatology)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Methotrexateの抗リウマチ効果に及ぼすポリグルタミン酸数の影響と効果発現機構の検討2018

    • Author(s)
      浅野奨太、鈴木真伍、清水美貴子、橋口正行、田村悦臣
    • Organizer
      第38回 日本臨床薬理学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト滑膜細胞を用いたMethotrexate-polyglutamates体の抗リウマチ効果およびその制御機構の解明2016

    • Author(s)
      鈴木真伍、清水美貴子、橋口正行、望月眞弓、田村悦臣
    • Organizer
      第37回 日本臨床薬理学会学術総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県・米子市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] 関節リウマチに対するプロバイオティクスの有用性とメトトレキサートとの相互作用の検討2016

    • Author(s)
      鈴木真伍、清水美貴子、松本光晴、袴田潤、橋口正行、望月眞弓、田村悦臣
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] プロバイオティクスのCYP3A4制御を介した脂質異常症治療の有用性の評価2016

    • Author(s)
      班目陽一、清水美貴子、松本光晴、田村悦臣
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト小腸でのビフィズズ菌によるBCRP発現制御機構の解明2015

    • Author(s)
      清水美貴子、鈴木真伍、村尾直彦、松本光晴、橋口正行、望月眞弓、田村悦臣
    • Organizer
      第36回日本臨床薬理学会学術総会
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 関節リウマチ患者におけるメトトレキサートの 治療反応性と遺伝子多型の関連のメタアナリシス2015

    • Author(s)
      袴田潤、橋口正行、清水 美貴子、丸山順也、望月眞弓
    • Organizer
      第18回 日本医薬品情報学会総会・学術大会
    • Place of Presentation
      岡山大学創立五十周年記念館(岡山県・岡山市)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2021-02-19  

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