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Effects of Exercise on the Oral Microbiota and Saliva of Patients With Non-Alcoholic Fatty Liver Disease

Research Project

Project/Area Number 20K11644
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Uchida Fumihiko  筑波大学, 医学医療系, 講師 (70736008)

Co-Investigator(Kenkyū-buntansha) 鈴木 英雄  筑波大学, 医学医療系, 准教授 (00400672)
呉 世昶  アール医療専門職大学, リハビリテーション学部, 教授 (10789639)
岡田 浩介  筑波大学, 医学医療系, 准教授 (80757526)
正田 純一  筑波大学, 医学医療系, 客員教授 (90241827)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肥満 / NAFLD / 歯周病 / 運動療法 / 口腔内細菌叢 / メタゲノム解析 / 肝線維化 / FAST score / 歯周病原菌種 / PISA / 細菌叢 / 脂肪性肝炎 / LPS / 運動実践 / クッパー細胞機能
Outline of Research at the Start

非アルコール性脂肪性肝炎 の要因の一つに歯周病の高い罹患率がある. 代表者は, 運動実践は肥満者の口腔内病変を改善し, 歯周病菌叢を変化させ, 肝ではKupffer細胞の異物貪食能とLPSクリアランスを増大させ, LPSによる自然免疫反応の活性化を抑止して炎症性肝障害を改善させる観察結果を得ている. そこで本研究では, 中高度肥満者に3ヶ月間の運動療法を実施する. その前後において採取した唾液および糞便中細菌叢のメタゲノム解析を実施し, 臨床データと比較検討する. 肥満者の口腔内dysbiosisの改善を介したNASH肝病態の改善とその分子メカニズムについて解明する.

Outline of Final Research Achievements

Biochemical and genetic analyses on saliva from overweight men with NAFLD and gum disease were done before and after 12-week exercise or diet programs. Importantly, we found that reductions in lactoferrin, lipopolysaccharide, and IgA concentrations were only evident in the men who followed the exercise regimen. The exercise group also showed increased bacterial diversity and changes in the relative constituent bacterial populations. In the overall population, more bacteria expressed genes related to environmental information processing, and less bacteria expressed genes related to genetic information processing and metabolism. In fact, bacteria expressed fewer genes for producing lipopolysaccharides.
It seems that, in people with both non-alcoholic liver disease and gum disease, exercise causes a biochemical shift in the environment of the mouth that favors the survival of less harmful bacteria.

Academic Significance and Societal Importance of the Research Achievements

本研究により, NAFLD肥満者について, 運動療法が口腔内の細菌叢の構成や唾液成分の変化を介して歯周病の改善をもたらすことが実証され, 肥満者, 糖尿病, 高齢者など歯周病の高リスクグループに対する健康管理の一環として, 運動療法の重要性がより明確になったと言うことが出来る.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results)

  • [Journal Article] Transplanted neural lineage cells derived from dental pulp stem cells promote peripheral nerve regeneration2022

    • Author(s)
      Takaoka S, Uchida F, Ishikawa H, Toyomura J, Ohyama A, Watanabe M, Matsumura H, Marushima A, Iizumi S, Fukuzawa S, Ishibashi-Kanno N, Yamagata K, Yanagawa T, Matsumaru Y, Bukawa H
    • Journal Title

      Hum Cell

      Volume: 35 Pages: 462-471

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA 142-5p promotes tumor growth in oral squamous cell carcinoma via the PI3K/AKT pathway by regulating PTEN2021

    • Author(s)
      Iizumi S, Uchida F, Nagai H, Takaoka S, Fukuzawa S, Kanno NI, Yamagata K, Tabuchi K, Yanagawa T, Bukawa H
    • Journal Title

      Heliyon

      Volume: 7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between the C-reactive protein/albumin ratio and prognosis in patients with oral squamous cell carcinoma2021

    • Author(s)
      Yamagata K, Fukuzawa S, Ishibashi-Kanno N, Uchida F, Bukawa H. Scientific reports
    • Journal Title

      Sci Reps

      Volume: 11 Pages: 5446-5446

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevention of non-alcoholic steatohepatitis by long-term exercise via the induction of phenotypic changes in Kupffer cells of hyperphagic obese mice2021

    • Author(s)
      Miura I, Komine S, Okada K, Wada S, Warabi E, Uchida F, Oh S, Suzuki H, Mizokami Y, Shoda J
    • Journal Title

      Physiol Reps

      Volume: 9

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Weight loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD. JHEP Reports 3: 100253, 2021 (IF: 7.468). DOI: 10.1016/j.jhepr.202021

    • Author(s)
      Oh S, Tsujimoto T, Kim B, Uchida F, Iizumi S, Isobe T, Sakae T, Tanaka K, Shoda J
    • Journal Title

      JHEP Reports

      Volume: 3 Pages: 100253-100253

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Weight loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD2021

    • Author(s)
      Oh S, Tsujimoto T, Kim B, Uchida F, Iizumi S, Isobe T, Sakae T, Tanaka K, Shoda J
    • Journal Title

      JHEP Reports

      Volume: 未定

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Exercise on the Oral Microbiota and Saliva of Patients with Non-Alcoholic Fatty Liver Disease2021

    • Author(s)
      Uchida F, Oh S, Shida T, Suzuki H, Yamagata K, Mizokami Y, Bukawa H, Tanaka K, Shoda J
    • Journal Title

      Int J Environ Res Public Health

      Volume: 18 Issue: 7 Pages: 3470-3470

    • DOI

      10.3390/ijerph18073470

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 転写因子Nrf2は歯周病菌関連非アルコール性脂肪性肝炎を防御する2022

    • Author(s)
      千原佳菜子、岡田浩介、内田文彦、福澤 智、菅野直美、山縣憲司、柳川 徹、武川寛樹
    • Organizer
      第76回 NPO法人 日本口腔科学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 歯周病の病態が非アルコール性脂肪性肝疾患(NAFLD)の肝線維化進展に与える影響2022

    • Author(s)
      千原佳菜子、福澤 智、菅野直美、柳川 徹
    • Organizer
      第32回 日本有病者歯科医療学会総会・学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝疾患 (NAFLD) における運動療法の重要性2021

    • Author(s)
      呉 世昶,森 祐太郎,磯部 智範,榮 武二,田中 喜代次,正田 純一
    • Organizer
      第11回肥満と消化器疾患研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 運動実践はKupffer細胞機能の改善と関連してNASHモデルp62遺伝子欠失マウスにおける脂肪性肝炎を改善する2021

    • Author(s)
      三浦 征,岡田 浩介,蕨 英治,正田 純一
    • Organizer
      第11回肥満と消化器疾患研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] Non-Alcoholic Fatty Liver Disease (NAFLD) における肝線維化進展と食品摂取頻度,身体活動状況との関連性2021

    • Author(s)
      矢部 義人,金 泰浩,正田 純一
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔がん患者における治療前栄養状態と予後の関係2021

    • Author(s)
      山縣憲司
    • Organizer
      第75回 日本口腔科学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔扁平上皮癌患者の予後予測における weighted lymph node ratio の有用性2021

    • Author(s)
      山縣憲司
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周病に対する運動の影響―口腔内細菌叢および唾液分析2020

    • Author(s)
      内田 文彦、廣畠 広実、福澤 智、菅野 直美、 山縣 憲司、武川 寛樹
    • Organizer
      第65回日本口腔外科学会総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 中年肥満男性の歯周病に対する運動療法の効果 口腔内細菌叢とメタゲノムの解析より2020

    • Author(s)
      内田 文彦、 志田 隆史、 大森 翔英、 呉 世昶、 福澤 智、 菅野 直美、 山縣 憲司、 鈴木 英雄、 正田 純一、 武川 寛樹
    • Organizer
      第74回日本口腔科学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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