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Integrated analysis of perio-systemic association based on the oral-gut connection

Research Project

Project/Area Number 15H02578
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontology
Research InstitutionNiigata University

Principal Investigator

Yamazaki Kazuhisa  新潟大学, 医歯学系, 教授 (00182478)

Co-Investigator(Kenkyū-buntansha) 加藤 完  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 特別研究員 (20632946)
大野 博司  国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (50233226)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥34,060,000 (Direct Cost: ¥26,200,000、Indirect Cost: ¥7,860,000)
Fiscal Year 2017: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2016: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2015: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Keywords口腔細菌 / 歯周病原細菌 / 腸内細菌 / 代謝性疾患 / dysbiosis / ペリオドンタルメディスン / 非感染性疾患 / 歯周病 / 関節リウマチ / 腸内細菌叢 / 全身疾患
Outline of Final Research Achievements

Epidemiological evidence suggests that periodontitis is associated with an increased risk of various diseases such as atherosclerotic vascular diseases and type 2 diabetes. Although bacteremia/endotoxemia and inflammatory mediators resulting from periodontitis lesion are hypothesized as underlying mechanisms by which periodontitis increases the risk of systemic diseases, there is not sufficient evidence to support the hypothesis. In this research project, we demonstrated that oral administration of P. gingivalis induced gut dysbiosis and systemic inflammation. Given that recent findings have implicated an altered gut microbiota as a contributor to various diseases with which periodontitis is also associated, it is reasonable to assume that the systemic inflammatory and metabolic changes seen in P. gingivalis-administered mice could be attributable to this altered gut microbiota. We propose this as a novel mechanism linking periodontal disease and systemic diseases.

Academic Significance and Societal Importance of the Research Achievements

これまで考えられてきた歯周病が全身疾患のリスクを高めるメカニズムには様々な矛盾点が含まれていた。本研究課題において、歯周病と関連する口腔細菌を多量、かつ継続的に嚥下することで腸内細菌が乱れ、それにより様々な全身疾患で見られる病理学的変化が誘導されることをはじめて示した。歯周病と全身疾患を関連づける新たなメカニズムとして口腸連関を世界で初めて提唱した。腸内細菌叢は全身の健康と密接に関連しており、歯周病治療が腸内細菌叢の改善を介して健康長寿に貢献することの学術的基盤を提供した意義は極めて大きい。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (35 results)

All 2018 2017 2016 2015 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 11 results,  Invited: 4 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Association of salivary lactate dehydrogenase level with systemic inflammation in a Japanese population2018

    • Author(s)
      Miyoshi N.、Tanigawa T.、Nishioka S.、Maruyama K.、Eguchi E.、Tanaka K.、Saito I.、Yamazaki K.、Miyake Y.
    • Journal Title

      Journal of Periodontal Research

      Volume: - Issue: 4 Pages: 487-494

    • DOI

      10.1111/jre.12537

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey2018

    • Author(s)
      Tabeta K.、Hosojima M.、Nakajima M.、Miyauchi S.、Miyazawa H.、Takahashi N.、Matsuda Y.、Sugita N.、Komatsu Y.、Sato K.、Ishikawa T.、Akiishi K.、Yamazaki K.、Kato K.、Saito A.、Yoshie H.
    • Journal Title

      Journal of Periodontal Research

      Volume: 印刷中 Issue: 3 Pages: 446-456

    • DOI

      10.1111/jre.12533

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system.2017

    • Author(s)
      Sato K, Takahashi N, Kato T, Matsuda Y, Yokoji M, Yamada M, Nakajima T, Kondo N, Endo N, Yamamoto R, Noiri Y, Ohno H, Yamazaki K
    • Journal Title

      Sci. Rep.

      Volume: 7(1) Issue: 1 Pages: 6955-6955

    • DOI

      10.1038/s41598-017-07196-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue.2017

    • Author(s)
      Tabeta K, Du X, Arimatsu K, Yokoji M, Takahashi N, Amizuka N, Hasegawa T, Crozat K, Maekawa T, Miyauchi S, Matsuda Y, Ida T, Kaku M, Hoebe K, Ohno K, Yoshie H, Yamazaki K, Moresco EMY, Beutler B
    • Journal Title

      Sci. Rep.

      Volume: 7(1) Issue: 1 Pages: 11717-11717

    • DOI

      10.1038/s41598-017-10343-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Resveratrol suppresses the alveolar bone resorption induced by artificial trauma from occlusion in mice2017

    • Author(s)
      Matsuda Y、Minagawa T、Okui T、Yamazaki K
    • Journal Title

      Oral Diseases

      Volume: 24 Issue: 3 Pages: 412-421

    • DOI

      10.1111/odi.12785

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Useful Immunochromatographic Assay of Calprotectin in Gingival Crevicular Fluid for Diagnosis of Diseased Sites in Patients with Periodontal Diseases2017

    • Author(s)
      Kido Jun-ichi、Murakami Shinya、Kitamura Masahiro、Yanagita Manabu、et al.
    • Journal Title

      Journal of Periodontology

      Volume: - Issue: 1 Pages: 1-19

    • DOI

      10.1902/jop.2017.170206

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ligature-induced periodontitis in mice induces elevated levels of circulating IL-6 but shows only weak effects on adipose and liver tissues.2016

    • Author(s)
      3.Matsuda Y, Kato T, Takahashi N, Nakajima M, Arimatsu K, Minagawa T, Sato K, Ohno H, Yamazaki K.
    • Journal Title

      Journal of Periodontal Research

      Volume: 51 Issue: 5 Pages: 639-646

    • DOI

      10.1111/jre.12344

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.2015

    • Author(s)
      4.Nakajima M, Arimatsu K, Kato T, Matsuda Y, Minagawa T, Takahashi N, Ohno H, Yamazaki K.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 7 Pages: 1-15

    • DOI

      10.1371/journal.pone.0134234

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A nove mechanism linking periodontitis and rheumatoid arthritis.2017

    • Author(s)
      Sato K, Takahashi N, Matsuda Y, Yamada M, Yokoji M, Tabeta K, Nakajima M, Yamazaki K.
    • Organizer
      95th General session of the IADR
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Year and Date
      2017-03-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A bacterial metabolite ameliorates P .gingivalis-induced gingival epithelial barrier disruption.2017

    • Author(s)
      Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Tabeta K, Nakajima T, Yamazaki K.
    • Organizer
      95th General session of the IADR
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Year and Date
      2017-03-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of resveratrol on alveolar bone loss induced by the experimental occlusal trauma in mice.2017

    • Author(s)
      Matsuda Y, Minagawa T, Okui T, Tabeta K, Nakajima T, Yamazaki K.
    • Organizer
      95th General session of the IADR
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Year and Date
      2017-03-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Pilot Study.2017

    • Author(s)
      Nakajima T., Miyazawa H., Horimizu M., Li L., Okada Y., Arita T., Inoue M., Nishida M., Yamazaki K., Genco RJ.
    • Organizer
      UNCPERIO 2017EXPO
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Periodontopathic bacteria increases the severity of collagen-induced arthritis by affecting gut microbiota.2017

    • Author(s)
      Yamazaki K, Sato K, Takahashi N, Kato T, Matsuda Y, Yokoji M, Yamada M, Yamazaki K, Nakajima T, Hiroshi Ohno.
    • Organizer
      PgMelbourne
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 歯周炎患者における腸内細菌叢の解析2017

    • Author(s)
      中島貴子,高橋直紀,皆川高嘉,宮沢春菜,伊藤晴江,佐藤圭祐,山崎和久
    • Organizer
      第60回春季日本歯周病学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of the association between alveolar bone resorption and atherosclerosis risk.2017

    • Author(s)
      Yonezawa D, Koide H, Aruga A, Takahasji S, Tsutsumi T, Kumagai S, Nakajima T and Yamazaki K.
    • Organizer
      12th Asian Pacific Society of Periodontology Meeting.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯周炎患者腸内細菌叢における口腔内由来細菌の比率2017

    • Author(s)
      山崎恭子,中島貴子,高橋直紀,宮沢春菜,皆川高嘉,佐藤圭祐,伊藤晴江,山崎和久
    • Organizer
      第147回日本歯科保存学会2017年度秋季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Porphyromonas gingivalis口腔投与のコラーゲン誘導性関節炎増悪メカニズムの解析2017

    • Author(s)
      佐藤圭祐、高橋直紀、中島麻由佳、松田由実、山田実生、横地麻衣、中島貴子、山崎和久
    • Organizer
      第147回日本歯科保存学会2017年度秋季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 塩酸ミノサイクリン局所投与がサポーティブペリオドンタルセラピー(SPT)期歯周炎患者の歯肉縁下細菌叢に及ぼす影響(第1報)2017

    • Author(s)
      中島貴子,宮沢春菜,堀水 慎,杉田典子,奥田一博,山崎和久
    • Organizer
      第147回日本歯科保存学会2017年度秋季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Benefitial role of a microbial metabolite on gingival epithelial barrier.2017

    • Author(s)
      Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Sulijaya B, Tabeta K, Nakajima T, Yamazaki K.
    • Organizer
      65th Annual meeting of JADR
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alveolar bone resorption and the risk factors for atherosclerosis among subjects who received general medical check-ups in Japan: Follow-up study of the Nagano Health Promotion Project.2017

    • Author(s)
      Yonezawa D, Koide H, Aruga A, Takahasji S, Tsutsumi T, Kumagai S, Yamazaki K, Nakajima T, and Yamazaki K.
    • Organizer
      65th Annual meeting of JADR
    • Related Report
      2017 Annual Research Report
  • [Presentation] 塩酸ミノサイクリン局所投与がサポーティブペリオドンタルセラピー(SPT)期歯周炎患者の歯肉縁下細菌叢に及ぼす影響(第2報)2017

    • Author(s)
      宮沢春菜,中島貴子,堀水 慎,杉田典子,奥田一博,山崎和久
    • Organizer
      第60回秋季日本歯周病学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 口腔細菌脂質代謝に由来する機能性脂肪酸HYAは歯肉上皮バリア機能の低下を抑制する.2016

    • Author(s)
      山田実生、高橋直紀、松田由実、佐藤圭祐、横地麻衣、多部田康一、中島貴子、山崎和久.
    • Organizer
      第59回秋季日本歯周病学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟県・新潟市)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Periodontopathic bacteria increases the risk of rheumatoid arthritis by affecting gut immune system.2016

    • Author(s)
      Sato K, Takahashi N, Nakajima M, Kato T, Matsuda Y, Yokoji M, Yamada M, Ohno H, Yamazaki K.
    • Organizer
      International Congress of Immunology 2016
    • Place of Presentation
      メルボルン(オーストラリア)
    • Year and Date
      2016-08-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 外傷性咬合により誘導される歯槽骨吸収に対するResveratrolの影響.2016

    • Author(s)
      松田由実、皆川高嘉、高橋直紀、佐藤圭祐、横地麻衣、山田実生、多部田康一、中島貴子,山崎和久.
    • Organizer
      第144回日本歯科保存学会2016年度春季学術大会
    • Place of Presentation
      栃木県総合文化センター(栃木県・宇都宮市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] Porphyromonas gingivalis口腔投与のコラーゲン誘導性関節炎増悪メカニズムの解析.2016

    • Author(s)
      佐藤圭祐、高橋直紀、中島麻由佳、松田由実、山田実生、横地麻衣、多部田康一、中島貴子、山崎和久
    • Organizer
      第59回春季日本歯周病学会学術大会
    • Place of Presentation
      鹿児島県文化センター(鹿児島県・鹿児島市)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] A novel mechanism linking periodontal disease and systemic diseases.2016

    • Author(s)
      Yamazaki K.
    • Organizer
      2nd International Forum on Periodontal disease in Asia.
    • Place of Presentation
      シンガポール(シンガポール)
    • Year and Date
      2016-01-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New Pardigm for the link between Periodontiti and Systemic Diseases.2015

    • Author(s)
      Yamazaki K.
    • Organizer
      6th Hiroshima Conference on Education and Science in Dentistry
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The effect of Prevotella intermedia administration on the systemic inflammation.2015

    • Author(s)
      Sato K, Takahashi N, Matsuda Y and Yamazaki K.
    • Organizer
      11th Asian Pacific Society of Periodontology Meeting
    • Place of Presentation
      デンパサール(インドネシア)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯周組織局所の炎症及びP. gingivalisによる腸内細菌叢の変動が全身に及ぼす影響とその分子機構の比較.2015

    • Author(s)
      松田由実、高橋直紀、有松 圭、中島麻由佳、佐藤圭祐、多部田康一、中島貴子、山崎和久
    • Organizer
      第58回秋季日本歯周病学会学術大会
    • Place of Presentation
      アクトシティ浜松(静岡県・浜松市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 歯周病が全身に及ぼす新たなメカニズム.2015

    • Author(s)
      山崎和久
    • Organizer
      第58回春季日本歯周病学会学術大会
    • Place of Presentation
      幕張メッセ(千葉県・千葉市)
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 歯周炎モデルマウスにおける腸内細菌叢の変動と免疫応答への影響.2015

    • Author(s)
      高橋直紀、有松 圭、中島麻由佳、松田由実、佐藤圭祐、多部田康一、中島貴子,加藤 完、大野博司、山崎和久.
    • Organizer
      第19回腸内細菌学会
    • Place of Presentation
      北里大学(東京都・港区)
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
  • [Book] The Human Microbiota and Chronic Disease: Dysbiosis as Cause of Human Pathology2016

    • Author(s)
      Kazuhisa Yamazaki
    • Total Pages
      18
    • Publisher
      John Wiley & Sons, Inc.
    • Related Report
      2016 Annual Research Report
  • [Book] ヒトマイクロバイオーム研究最前線2016

    • Author(s)
      山崎和久
    • Total Pages
      12
    • Publisher
      株式会社エヌ・ティー・エス
    • Related Report
      2015 Annual Research Report
  • [Book] 腸内細菌・口腔細菌と全身疾患2015

    • Author(s)
      高橋直紀・山崎和久
    • Total Pages
      9
    • Publisher
      シーエムシー出版
    • Related Report
      2015 Annual Research Report
  • [Remarks] 山崎研究室

    • URL

      http://www.dent.niigata-u.ac.jp/yamazaki_labo/

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report 2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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