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Elucidation of oral-gut association based on Elucidation of oral-gut association based on multi-omics analyzes

Research Project

Project/Area Number 18H04067
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionNiigata University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 大野 博司  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50233226)
奥田 修二郎  新潟大学, 医歯学系, 准教授 (00512310)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2020: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2019: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2018: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Keywords歯周病 / 口腔細菌 / 腸内細菌 / オーミクス解析 / 口ー腸連関 / 歯周病原細菌
Outline of Final Research Achievements

In order to clarify the mechanistic relationship between periodontal disease and systemic diseases based on the oral-gut connection, two experimental models; namely periodontopathic bacteria-administered non-alcoholic fatty liver disease mice and ligature-induced periodontitis in fecal microbiota transplantation (FMT) from obese mice were developed. In addition to the tissue pathologies, microbiome, metabolome and transcriptome analyzes were performed. The results demonstrated that oral gavage of periodontopathic bacteria, particularly Porphyromonas gingivalis worsened NAFLD by inducing alteration of gut microbiota composition and metabolomic profiles of serum and gut microbiota. FMT of obese mice deteriorated periodontal tissue destruction by changing the serum metabolomic profile.

Academic Significance and Societal Importance of the Research Achievements

歯周炎は様々な全身疾患のリスクを高めることが明らかになっているがそのメカニズムは解明されていない。我々は嚥下された歯周病原細菌が腸内細菌叢を変化させることが原因の一つであることを示した。本研究課題では病態モデルを作成し、歯周病原細菌は腸内細菌の代謝を変化させることで代謝性疾患に関連するアミノ酸代謝に影響を与えること、並びに肥満を模した腸内細菌叢はプリン代謝に影響を与えることで歯周炎における組織破壊を亢進させることを初めて明らかにした。これらの結果は、プロバイオティクスや細菌代謝物による新たな治療法の開発に繋がるものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (45 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 8 results) Presentation (28 results) (of which Int'l Joint Research: 7 results,  Invited: 13 results) Book (2 results)

  • [Journal Article] Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice2021

    • Author(s)
      Tsuzuno Takahiro、Takahashi Naoki、Yamada‐Hara Miki、Yokoji‐Takeuchi Mai、Sulijaya Benso、Aoki‐Nonaka Yukari、Matsugishi Aoi、Katakura Kyoko、Tabeta Koichi、Yamazaki Kazuhisa
    • Journal Title

      Journal of Periodontal Research

      Volume: 56 Issue: 2 Pages: 275-288

    • DOI

      10.1111/jre.12816

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A bacterial metabolite induces Nrf2-mediated anti-oxidative responses in gingival epithelial cells by activating the MAPK signaling pathway2020

    • Author(s)
      Yokoji-Takeuchi Mai、Takahashi Naoki、Yamada-Hara Miki、Sulijaya Benso、Tsuzuno Takahiro、Aoki-Nonaka Yukari、Tabeta Koichi、Kishino Shigenobu、Ogawa Jun、Yamazaki Kazuhisa
    • Journal Title

      Archives of Oral Biology

      Volume: 110 Pages: 104602-104602

    • DOI

      10.1016/j.archoralbio.2019.104602

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Orally administered pathobionts and commensals have comparable and innocuous systemic effects on germ-free mice2020

    • Author(s)
      Yamazaki Kyoko、Sato Keisuke、Tsuzuno Takahiro、Sulijaya Benso、Mashima Izumi、Kawamura Yoshiaki、Yamazaki Kazuhisa
    • Journal Title

      Microbial Pathogenesis

      Volume: 140 Pages: 103962-103962

    • DOI

      10.1016/j.micpath.2020.103962

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lactobacillus-Derived Bioactive Metabolites for the Regulation of Periodontal Health: Evidences to Clinical Setting2020

    • Author(s)
      Sulijaya Benso、Takahashi Naoki、Yamazaki Kazuhisa
    • Journal Title

      Molecules

      Volume: 25 Issue: 9 Pages: 2088-2088

    • DOI

      10.3390/molecules25092088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study2020

    • Author(s)
      Miyazawa Haruna、Nakajima Takako、Horimizu Makoto、Okuda Kazuhiro、Sugita Noriko、Yamazaki Kyoko、Li Lu、Hayashi-Okada Yoshiko、Arita Takuya、Nishimoto Misa、Nishida Mieko、Genco Robert、Yamazaki Kazuhisa
    • Journal Title

      Dentistry Journal

      Volume: 8 Issue: 4 Pages: 123-123

    • DOI

      10.3390/dj8040123

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 口-腸連関を基盤とした歯周病と全身疾患の関連メカニズム2020

    • Author(s)
      山崎和久
    • Journal Title

      日本未病学会雑誌

      Volume: 26 Pages: 38-42

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Indirect regulation of PCSK9 gene in inflammatory response by Porphyromonas gingivalis infection.2019

    • Author(s)
      Yokoji-Takeuchi M, Tabeta K, Takahashi N, Arimatsu K, Miyazawa H, Matsuda-Matsukawa Y, Sato K, Yamada M, Yamazaki K.
    • Journal Title

      Heliyon

      Volume: 5(1) Issue: 1 Pages: e01111-e01111

    • DOI

      10.1016/j.heliyon.2018.e01111

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Can oral bacteria affect the microbiome of the gut?2019

    • Author(s)
      Olsen Ingar、Yamazaki Kazuhisa
    • Journal Title

      Journal of Oral Microbiology

      Volume: 11 Issue: 1 Pages: 1586422-1586422

    • DOI

      10.1080/20002297.2019.1586422

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nutrition as Adjunct Therapy in Periodontal Disease Management2019

    • Author(s)
      Sulijaya Benso、Takahashi Naoki、Yamazaki Kyoko、Yamazaki Kazuhisa
    • Journal Title

      Current Oral Health Reports

      Volume: 6 Issue: 2 Pages: 61-69

    • DOI

      10.1007/s40496-019-0216-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis2019

    • Author(s)
      Sulijaya Benso、Yamada‐Hara Miki、Yokoji‐Takeuchi Mai、Matsuda‐Matsukawa Yumi、Yamazaki Kyoko、Matsugishi Aoi、Tsuzuno Takahiro、Sato Keisuke、Aoki‐Nonaka Yukari、Takahashi Naoki、Kishino Shigenobu、Ogawa Jun、Tabeta Koichi、Yamazaki Kazuhisa
    • Journal Title

      Journal of Periodontology

      Volume: 90 Issue: 12 Pages: 1470-1480

    • DOI

      10.1002/jper.19-0130

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Experimental arthritis and Porphyromonas gingivalis administration synergistically decrease bone regeneration in femoral cortical defects2019

    • Author(s)
      Okumura Go、Kondo Naoki、Sato Keisuke、Yamazaki Kazuhisa、Ohshima Hayato、Kawashima Hiroyuki、Ogose Akira、Endo Naoto
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20031-20031

    • DOI

      10.1038/s41598-019-56265-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The anti-inflammatory effect of 10-oxo-trans-11-octadecenoic acid (KetoC) on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide2018

    • Author(s)
      Sulijaya B.、Takahashi N.、Yamada M.、Yokoji M.、Sato K.、Aoki-Nonaka Y.、Nakajima T.、Kishino S.、Ogawa J.、Yamazaki K.
    • Journal Title

      Journal of Periodontal Research

      Volume: 印刷中 Issue: 5 Pages: 777-784

    • DOI

      10.1111/jre.12564

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling2018

    • Author(s)
      Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Sulijaya B, Maekawa T, Ushiki T, Mikami Y, Hayatsu M, Mizutani Y, Kishino S, Ogawa J, Arita M, Tabeta K, Maeda T, Yamazaki K
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 9008-9008

    • DOI

      10.1038/s41598-018-27408-y

    • NAID

      120006546008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ-free mice2018

    • Author(s)
      Sato Keisuke、Yokoji Mai、Yamada Miki、Nakajima Takako、Yamazaki Kazuhisa
    • Journal Title

      Journal of Periodontal Research

      Volume: 53 Issue: 6 Pages: 950-960

    • DOI

      10.1111/jre.12593

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral Administration of Porphyromonas gingivalis Alters the Gut Microbiome and Serum Metabolome2018

    • Author(s)
      Kato Tamotsu、Yamazaki Kyoko、Nakajima Mayuka、Date Yasuhiro、Kikuchi Jun、Hase Koji、Ohno Hiroshi、Yamazaki Kazuhisa
    • Journal Title

      mSphere

      Volume: 3 Issue: 5 Pages: 1-11

    • DOI

      10.1128/msphere.00460-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 口‐腸連関から考える歯周病と全身の関係2020

    • Author(s)
      山崎和久
    • Organizer
      第63回秋季日本歯周病学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Oral-gut microbiome axis and its role in the periodontal and systemic interrelationship2020

    • Author(s)
      Kazuhisa Yamazaki
    • Organizer
      106th Annual meeting AAP
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 歯周病はどのようにして全身の健康を脅かすのか?2020

    • Author(s)
      山崎和久
    • Organizer
      第11回日本歯科衛生教育学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 歯周病が全身及ぼす悪影響ー新たなメカニズムー2020

    • Author(s)
      山崎和久
    • Organizer
      第20回日本口腔ケア協会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Germ-free環境における歯周病原細菌群と口腔共生菌群経口投与が全身に与える影響の比較2020

    • Author(s)
      山崎恭子,佐藤圭祐,都野隆博,山崎和久
    • Organizer
      第63回春季日本歯周病学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 歯周炎患者における腸内細菌叢の解析2020

    • Author(s)
      山崎恭子,中島貴子,宮沢春菜,伊藤晴江,佐藤圭祐,原 実生,竹内麻衣,高橋直紀,森田英利,須田 亙,服部正平,山崎和久
    • Organizer
      第23回腸内細菌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 口-腸連関から考える歯周病の全身への影響.シンポジウム17:加齢に伴う口腔環境の変化と全身疾患.2019

    • Author(s)
      山崎和久
    • Organizer
      第73回日本栄養・食料学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Oral-gut axis as a causal mechanism for periodontal-systemic associations.2019

    • Author(s)
      Kazuhisa Yamazaki
    • Organizer
      IAP-JSP symposium at IAP2019 The 17th Biennial Conference of IAP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口-腸連関に基づくPeriodontal medicine病因論2019

    • Author(s)
      山崎和久
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Oral-gut connection as a mechanism for the association between periodontal disease and systemic diseases.2019

    • Author(s)
      Kazuhisa Yamazaki
    • Organizer
      4th meeting of the IADR-APR 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口‐腸連関を基盤とした歯周病と全身疾患の関連メカニズム2019

    • Author(s)
      山崎和久
    • Organizer
      第26回日本未病システム学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌の変動が歯周炎の発症・進行に与える影響の解析2019

    • Author(s)
      佐藤圭祐,松川由実,原 実生,竹内麻衣,都野隆博,松岸 葵,山崎恭子,多部田康一,山崎和久
    • Organizer
      第62回春季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Porphyromonas gingivalisがNASH病態に与える影響の解析2019

    • Author(s)
      山崎恭子,中島麻由佳,竹内麻衣,原 実生,都野隆博,松岸 葵,松川由実,佐藤圭祐,高橋直紀,多部田康一,山崎和久
    • Organizer
      第62回春季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Porphyromonas gingivalis口腔投与がDSS誘導性実験的腸炎に及ぼす影響の解析2019

    • Author(s)
      都野隆博,高橋直紀,竹内麻衣,原 実生,中島麻由佳,多部田康一,山崎和久
    • Organizer
      第62回春季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Porphyromonas gingivalisが腸管バリア機能へ及ぼす影響の解析2019

    • Author(s)
      都野隆博,高橋直紀,竹内麻衣,原 実生,中島麻由佳,多部田康一,山崎和久
    • Organizer
      日本歯科保存学会2019年度春季学術大会(第150回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 実験的腸炎モデルマウスにおけるPorphyromonas gingivalisによる腸炎増悪メカニズムの解析2019

    • Author(s)
      都野隆博,高橋直紀,竹内麻衣,原 実生,多部田康一,山崎和久
    • Organizer
      第62回秋季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 歯周炎患者唾液細菌叢が腸内細菌叢にあたえる影響の解析2019

    • Author(s)
      山崎恭子,中島貴子,宮沢春菜,伊藤晴江,佐藤圭祐,原 実生,竹内麻衣,高橋直紀,森田英利,須田 亙,服部正平,山崎和久
    • Organizer
      第62回秋季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Porphyromonas gingivalisがNASH病態を進行させるメカニズムの解析2019

    • Author(s)
      山崎恭子,中島麻由佳,竹内麻衣,原 実生,都野隆博,松岸 葵,松川由美,佐藤圭祐,高橋直紀,多部田 康一,山崎和久
    • Organizer
      日本歯科保存学会2019年度秋季学術大会(第151回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規機能性脂肪酸の歯肉上皮細胞における抗酸化ストレス作用の検討2018

    • Author(s)
      横地 麻衣,高橋 直紀,松田 由美,山田 実生,Benso Sulijaya,多部田 康一,中島 貴子,山崎 和久
    • Organizer
      第61回春季日本歯周病学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Porphyromonas gingivalis口腔投与が無菌マウスに与える影響の解析2018

    • Author(s)
      佐藤 圭祐,山田 実生,横地 麻衣,中島 貴子,山崎 和久
    • Organizer
      第61回春季日本歯周病学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口腔細菌叢のdysbiosisと全身の健康との関わり2018

    • Author(s)
      山崎和久
    • Organizer
      日本口腔科学会第12回教育研修会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Bioactive metabolite inhibits proinflammatory cytokines by macrophage treated with Porphyromonas gingivalis lipopolysaccharide via G-protein-coupled receptor 1202018

    • Author(s)
      Benso Sulijaya, Naoki Takahashi, Miki Yamada, Mai Yokoji, Keisuke Sato, Yukari Aoki-Nonaka, Takako Nakajima, Kazuhisa Yamazaki
    • Organizer
      第61回春季日本歯周病学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口-腸-全身軸:ペリオドンタルメディスンの新たな因果メカニズム2018

    • Author(s)
      山崎和久
    • Organizer
      日本臨床歯周病学会第36回年次大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Preventive Effect of Microbial Metabolite on Periodontitis in Mice2018

    • Author(s)
      Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Sulijaya B, Tabeta K, Nakajima T, Yamazaki K
    • Organizer
      96th General session of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Anti-Oxidative Function of 10-Oxo-trans-11-octadecenoic Acid in Gingival Epithelial Cells2018

    • Author(s)
      Yokoji M, Takahashi N, Matsuda Y, Yamada M, Sulijaya B, Tabeta K, Nakajima T, Yamazaki K
    • Organizer
      96th General session of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 10-Hydroxy-cis-12-Octadecenoic Acid Ameliorates Gingival Epithelial Barrier Disruption via GPR40-ERK Signaling2018

    • Author(s)
      Takahashi N, Yamada M, Matsuda Y, Sato K, Yokoji M, Sulijaya B, Tabeta K, Nakajima T, Maeda T, Yamazaki K
    • Organizer
      96th General session of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oral-gut connection is a new paradigm of periodontal medicine2018

    • Author(s)
      Kazuhisa Yamazaki
    • Organizer
      The 5th National Scientific Seminar in Periodontics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口‐腸連関を基軸とした歯周病と全身の関連2018

    • Author(s)
      山崎和久
    • Organizer
      第24回Hindgut Club Japan
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] ヒトマイクロバイオーム Vol.22020

    • Author(s)
      服部正平
    • Total Pages
      624
    • Publisher
      NTS
    • Related Report
      2020 Annual Research Report
  • [Book] ヒト常在菌叢と生理機能・全身疾患2020

    • Author(s)
      落合邦康
    • Total Pages
      325
    • Publisher
      シーエムシー出版
    • ISBN
      9784781315195
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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