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Establishment of a method to prevent the development of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma by focusing on periodontal disease and oral microflora.

Research Project

Project/Area Number 19K10454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57080:Social dentistry-related
Research InstitutionKanagawa Dental College

Principal Investigator

Minabe Masato  神奈川歯科大学, その他部局等, 特任教授 (60148004)

Co-Investigator(Kenkyū-buntansha) 両角 俊哉  日本歯科大学, 新潟生命歯学部, 教授 (20444151)
中島 淳  横浜市立大学, 医学研究科, 教授 (30326037)
結束 貴臣  横浜市立大学, 附属病院, 講師 (30738620)
宮内 睦美  広島大学, 医系科学研究科(歯), 教授 (50169265)
山本 裕子  神奈川歯科大学短期大学部, その他部局等, 准教授 (60756568)
鎌田 要平  神奈川歯科大学, 歯学部, 講師 (80385070)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords非アルコール性脂肪性肝炎 / 非アルコール性脂肪性肝炎由来肝細胞がん / 歯周病 / Porphyromonas gingivalis / Fusobacterium nucleatum / 非アルコール性肝炎由来肝がん / 歯周病原細菌 / 腸内細菌 / 非アルコール性脂肪性肝炎由来肝がん / 腸内細菌叢 / 唾液 / IgA / 口腔内細菌叢 / 唾液中IgA分泌速度 / 肝がん / 非アルコール性脂肪性肝疾患
Outline of Research at the Start

1.非アルコール性脂肪性肝炎(NASH)由来肝がんを発症した患者の歯周病の病態を解明する 2019年・2020年
2.NASH由来肝がんを発症した患者におけPorphyromonas gingivalis(P.g.)感染との関係を解明する 2019年・2020年
3.NASH患者の肝臓の病態と口腔内細菌叢・腸内細菌叢の関係を検討する 2021年

Outline of Final Research Achievements

We analyzed oral and gut microbiota data in patients with metabolic dysfunction-associated steatohepatitis (MASH) and MASH-derived hepatocellular carcinoma (MASH-HCC) to examine the association between MASH-HCC and periodontal pathogenic bacteria. Results of causal Bayesian network analysis indicated that HCC may affect oral periodontopathogenic bacteria and fecal bacteria. In addition, Porphyromonas gingivalis (P.g.) indirectly affected fecal Blautia and Butyricoccu genera in MASH and MASH-HCC patients. This study indicates that oral P.g. may have an indirect effect on intestinal bacteria associated with HCC.

Academic Significance and Societal Importance of the Research Achievements

現在の日本では、肥満や食生活の乱れに起因する非アルコール性脂肪性肝炎(MASH)を背景とした肝がん(MASH-HCC)が増加し社会問題となっている。しかしながら生活習慣の改善以外に有効な治療法が確立されておらず、早急かつ効果的な対応策が求められている。近年MASH発症の一要因に、歯周病原細菌の感染が関与している可能性が報告され、歯周病とMASHの関係解明が期待されている。本研究は歯周病原細菌がMASH-HCC発症に与える影響を解析したものである。将来的には歯周病治療と口腔内細菌叢を介した「歯科から発信する新しいMASH-HCC発症予防法」を構築し、国の医療費削減に貢献できる可能性がある。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (10 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Does the Restoration of Masticatory Function by Periodontal Treatment Contribute to Improving Glycemic Control?2024

    • Author(s)
      三辺 正人、山本 裕子、河野 寛二、中澤 正絵、山本 龍生
    • Journal Title

      The Japanese Journal of Conservative Dentistry

      Volume: 67 Issue: 1 Pages: 10-19

    • DOI

      10.11471/shikahozon.67.10

    • ISSN
      0387-2343, 2188-0808
    • Year and Date
      2024-02-29
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma and Periodontopathic Bacteria: A Cross-Sectional Pilot Study2023

    • Author(s)
      Takuma Ryo、Morozumi Toshiya、Yamamoto Yuko、Kobayashi Takashi、Matsui Takaaki、Yoneda Masato、Kessoku Takaomi、Nogami Asako、Tamura Muneaki、Kamata Yohei、Sugihara Shuntaro、Nomura Yoshiaki、To Masahiro、Minabe Masato、Mitsudo Kenji、Nakajima Atsushi、Komaki Motohiro
    • Journal Title

      Applied Sciences

      Volume: 13 Issue: 6 Pages: 3893-3893

    • DOI

      10.3390/app13063893

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 医科歯科チーム医療による歯周病糖尿病合併患者の連携診療の必要性.2022

    • Author(s)
      平田貴久, 両角俊哉, 栗林伸一, 三邉正人
    • Journal Title

      日本口腔検査学会雑誌

      Volume: 14(1) Pages: 3-8

    • Related Report
      2021 Research-status Report
  • [Journal Article] 循環器疾患患者におけるプロービング時の出血の有無と全身的因子の関連の検討.2021

    • Author(s)
      青山典生,呉 圭哲,藤井利哉,喜田さゆり,髙瀬雅大,杉原俊太郎,門田大地,三邉正人
    • Journal Title

      日本歯科保存学雑誌

      Volume: 64(2) Pages: 163-170

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Estimation of the Periodontal Inflamed Surface Area by Simple Oral Examination2021

    • Author(s)
      Nomura Y, Morozumi T*, Numabe Y, Ogata Y, Nakayama Y, Sugaya T, Nakamura T, Sato S, Takashiba S, Sekino S, Yoshinari N, Hanada N, Sugano N, Fukuda M, Minabe M, Umeda M, Tabeta K, Takahashi K, Noguchi K, Kobayashi H, Takai H, Nishimura F, Suzuki F, Kakuta E, Yoshimura A, Saito A, Nakagawa T
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 4 Pages: 723-723

    • DOI

      10.3390/jcm10040723

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prospective Longitudinal Changes in the Periodontal Inflamed Surface Area Following Active Periodontal Treatment for Chronic Periodontitis2021

    • Author(s)
      Nomura Y, Morozumi T*, Saito A, Yoshimura A, Kakuta E, Suzuki F, Nishimura F, Takai H, Kobayashi H, Noguchi K, Takahashi K, Tabeta K, Umeda M, Minabe M, Fukuda M, Sugano N, Hanada N, Yoshinari N, Sekino S, Takashiba S, Sato S, Nakamura T, Sugaya T, Nakayama Y, Ogata Y, Numabe Y, Nakagawa T
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 6 Pages: 1165-1165

    • DOI

      10.3390/jcm10061165

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Periodontal Disease on Diabetic Retinopathy in Type 2 Diabetic Patients: A Cross-Sectional Pilot Study2020

    • Author(s)
      Yamamoto Yuko、Morozumi Toshiya、Hirata Takahisa、Takahashi Toru、Fuchida Shinya、Toyoda Masami、Nakajima Shigeru、Minabe Masato
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 10 Pages: 3234-3234

    • DOI

      10.3390/jcm9103234

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model2020

    • Author(s)
      Nomura Y, Morozumi T*, Fukuda M, Hanada N, Kakuta E, Kobayashi H, Minabe M, Nakamura T, Nakayama Y, Nishimura F, Noguchi K, Numabe Y, Ogata Y, Saito A, Sato S, Sekino S, Sugano N, Sugaya T, Suzuki F, Takahashi K, Takai H, Takashiba S, Umeda M, Yoshie H, Yoshimura A, Yoshinari N, Nakagawa T
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 11 Pages: 3754-3754

    • DOI

      10.3390/jcm9113754

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial2020

    • Author(s)
      Kamata Yohei、Kessoku Takaomi、Shimizu Tomoko、Kobayashi Takashi、Kurihashi Takeo、Sato Satsuki、Kuraji Syotaro、Aoyama Norio、Iwasaki Tomoyuki、Takashiba Shogo、Hamada Nobushiro、Kodama Toshiro、Tamura Toshiyuki、Ino Satoshi、Higurashi Takuma、Taguri Masataka、Yamanaka Takeharu、Yoneda Masato、Minabe Masato
    • Journal Title

      Trials

      Volume: 21 Issue: 1 Pages: 291-291

    • DOI

      10.1186/s13063-020-4201-y

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased Heart Failure Prevalence in Patients with a High Antibody Level Against Periodontal Pathogen2019

    • Author(s)
      Aoyama N, Kure K, Minabe M, Izumi Y.
    • Journal Title

      International Heart Journal

      Volume: 60 Issue: 5 Pages: 1142-1146

    • DOI

      10.1536/ihj.19-010

    • NAID

      130007718936

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2019-09-27
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Urinary Albumin Excretion With Periodontal Parameters in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study2019

    • Author(s)
      Tanaka M, Yamamoto T, Kuribayashi N, Okuguchi F, Isotani H, Iwamoto M, Sugimoto H, Nakagawa O, Suzuki D, Abe K, Watanabe N, Minabe M, Fuchida S, Yokoyama H.
    • Journal Title

      Diabetology International

      Volume: 11(2) Issue: 2 Pages: 121-128

    • DOI

      10.1007/s13340-019-00413-w

    • NAID

      40022198981

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological responses following one‐stage full‐mouth scaling and root planing with and without azithromycin: Multicenter randomized trial2019

    • Author(s)
      Yashima Akihiro、Morozumi Toshiya、Yoshie Hiromasa、Hokari Takahiro、Izumi Yuichi、Akizuki Tatsuya、Mizutani Koji、Takamatsu Hideyuki、Minabe Masato、Miyauchi Satomi、Yoshino Toshiaki、Tanaka Maki、Tanaka Yoshie、Gomi Kazuhiro
    • Journal Title

      Journal of Periodontal Research

      Volume: 54 Issue: 6 Pages: 709-719

    • DOI

      10.1111/jre.12680

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory Effects of Azithromycin on the Adherence Ability of Porphyromonas Gingivalis2019

    • Author(s)
      Kan P, Sasaki H, Inaba K, Watanabe K, Hamada N, Minabe M.
    • Journal Title

      Journal of Periodontology

      Volume: 90(8) Issue: 8 Pages: 903-910

    • DOI

      10.1002/jper.18-0559

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 非アルコール性脂肪性肝炎由来幹細胞がんにおける歯周病の関与2022

    • Author(s)
      琢磨遼, 両角俊哉, 松井嵩昌, 山本裕子, 結束貴臣, 米田正人, 野上麻子, 小林貴, 杉原俊太郎, 鎌田要平, 田村宗明, 光藤健司, 中島淳, 三邉正人, 小牧基浩
    • Organizer
      歯周病の関与:第65回秋季日本歯周病学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 医科歯科連携による歯周病と糖尿病のスクリーニング検査及びその有用性の検討2021

    • Author(s)
      平田貴久, 両角俊哉, 杉原俊太郎, 門田大地,青木一孝,三邉正人
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周炎症面積と歯数および肥満の関連2021

    • Author(s)
      青山典生,藤井利哉,喜田さゆり,谷口健太郎,野澤一郎太,藤原基,岩根泰蔵,玉置勝司,三邉正人
    • Organizer
      第64回春季日本歯周病学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周病評価における最適検査部位の選定 ―項目反応理論 Graded response modelの応用―2021

    • Author(s)
      両角俊哉, 野村義明, 福田光男, 花田信弘, 角田衣理加, 小林宏明, 三邉正人, 中村利明, 中 山洋平, 西村英紀, 野口和行, 沼部幸博, 小方頼昌, 齋藤 淳, 佐藤 聡, 関野 諭, 菅野直之, 菅谷 勉, 鈴木史彦, 多部田康一, 高橋慶壮, 高井英樹, 高柴正悟, 梅田 誠, 吉江弘正, 吉村 篤利, 吉成伸夫, 中川種昭
    • Organizer
      第64回春季日本歯周病学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周病のポケット選定における代表歯・部位の選定2021

    • Author(s)
      両角俊哉, 高柴正悟, 三邉正人, 野村義明, 福田光男, 花田信弘, 角田衣理加, 小林宏明,中 村利明, 中山洋平, 西村英紀, 野口和行, 沼部幸博, 小方頼昌, 齋藤 淳, 佐藤 聡, 関野 諭, 菅野直之, 菅谷 勉, 鈴木史彦, 多部田康一, 高橋慶壮, 高井英樹,梅田 誠, 吉江弘正, 吉村 篤利, 吉成伸夫, 中川種昭
    • Organizer
      第14回日本口腔検査学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] PISAを用いた全身疾患リスク評価の検討2021

    • Author(s)
      藤井利哉, 青山典生, 谷口健太郎, 喜田さゆり, 張宇安, 矢田朋美, 野澤一郎太, 玉置勝司, 三邉正人
    • Organizer
      第64回秋季日本歯周病学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Associations among periodontal status, oral frailty and general condition.2019

    • Author(s)
      Aoyama N,Fujii T,Fujiwara M,Tamaki K,Minabe M
    • Organizer
      13th Asian Pacific Society of Periodontology Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased level of periodontal inflamed surface area in obese Japanese population.2019

    • Author(s)
      Aoyama N,Fujii T,Fujiwara M,Haruta M,Takuma R,Kida S,Tamaki K,Minabe M
    • Organizer
      The American Academy of Periodontology 105th annual meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Association between periodontitis and hypertension in the member of the Japan Maritime Self-Defense Forces.2019

    • Author(s)
      Takase M,Aoyama N,Ebisawa N,Kato H,Minabe M
    • Organizer
      The American Academy of Periodontology 105th annual meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神奈川歯科大学附属病院医科歯科連携センターにおける口腔と全身疾患発症予防を目指した各種検査の概要2019

    • Author(s)
      三辺正人,青山典生,藤井利哉,山本裕子,春田真穂,岩根泰蔵,玉置勝司
    • Organizer
      第19回日本抗加齢医学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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