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Next step in the oral-gut connection: Do swallowed periodontopathogenic bacteria exacerbate colitis?

Research Project

Project/Area Number 19K10126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionNiigata University

Principal Investigator

Takahashi Naoki  新潟大学, 医歯学系, 准教授 (80722842)

Co-Investigator(Kenkyū-buntansha) 多部田 康一  新潟大学, 医歯学系, 教授 (20401763)
片倉 響子  福島県立医科大学, 医学部, 講師 (70423788)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsペリオドンタルメディスン / 歯周病 / 実験的腸炎モデルマウス / 上皮バリア / P. gingivalis / 歯周病原細菌 / 潰瘍性腸炎 / 歯周炎 / 炎症性腸疾患 / 腸管上皮細胞
Outline of Research at the Start

我々はこれまでに嚥下された歯周病原細菌が腸内細菌叢を攪乱することで全身性に悪影響をおよぼすことを明らかにし,口腔-腸管連関によるペリオドンタルメディスンの新規病因論を提案した.しかしながら,潰瘍性大腸炎をはじめとする炎症性腸疾患に対する口腔細菌の直接的な影響は不明である.そこで本研究の目的は,嚥下された口腔細菌が炎症性腸疾患におよぼす影響とそのメカニズムについて検証することで,口腔内プロバイオティクスを用いた炎症性腸疾患の予防や治療法,口腔内細菌検査による腸炎リスク評価法の確立を目指すものである.

Outline of Final Research Achievements

This study aimed to evaluate the effects of ingested periodontal pathogens on experimental colitis in mice and to elucidate its underlying mechanisms. We found that the oral administration of P. gingivalis significantly increased the severity of colitis when compared to other pathogens in the DSS-induced colitis model.
The ingested P. gingivalis disrupted the colonic epithelial barrier by decreasing the expression of tight junction proteins in vivo. In vitro permeability assays using the intestinal epithelial cell line suggested the P. gingivalis-specific epithelial barrier disruption. The possible involvement of gingipains in the exacerbation of colitis was implied by using P. gingivalis lacking gingipains.

Academic Significance and Societal Importance of the Research Achievements

今回の薬剤誘導性実験的腸炎モデルマウスを用いた一連の研究において、経口投与されたP. gingivalisが腸管上皮バリア機能の破綻を介して腸炎重症化に関与することが確認されたことから、歯周炎が炎症性腸疾患に悪影響を与えることが示唆された。そのメカニズムのひとつとして、P. gingivalis由来のプロテアーゼgingipainの関与が示唆されたことから、炎症性腸疾患の重症化予防や治療におけるプロテアーゼ阻害薬を用いた創薬が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (38 results)

All 2021 2020 2019

All Journal Article (19 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 19 results,  Open Access: 12 results) Presentation (18 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Book (1 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
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Erythromycin on Osteoclasts and Bone Resorption via DEL-1 Induction in Mice2021

    • Author(s)
      Tamura Hikaru、Maekawa Tomoki、Domon Hisanori、Hiyoshi Takumi、Hirayama Satoru、Isono Toshihito、Sasagawa Karin、Yonezawa Daisuke、Takahashi Naoki、Oda Masataka、Maeda Takeyasu、Tabeta Koichi、Terao Yutaka
    • Journal Title

      Antibiotics

      Volume: 10 Issue: 3 Pages: 312-312

    • DOI

      10.3390/antibiotics10030312

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rice bran-derived protein fractions enhance sulforaphane-induced anti-oxidative activity in gingival epithelial cells2021

    • Author(s)
      Mineo Shuhei、Takahashi Naoki、Yamada-Hara Miki、Tsuzuno Takahiro、Aoki-Nonaka Yukari、Tabeta Koichi
    • Journal Title

      Archives of Oral Biology

      Volume: 129 Pages: 105215-105215

    • DOI

      10.1016/j.archoralbio.2021.105215

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice2021

    • Author(s)
      Yamazaki Kyoko、Kato Tamotsu、Tsuboi Yuuri、Miyauchi Eiji、Suda Wataru、Sato Keisuke、Nakajima Mayuka、Yokoji-Takeuchi Mai、Yamada-Hara Miki、Tsuzuno Takahiro、Matsugishi Aoi、Takahashi Naoki、Tabeta Koichi、Miura Nobuaki、Okuda Shujiro、Kikuchi Jun、Ohno Hiroshi、Yamazaki Kazuhisa
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 766170-766170

    • DOI

      10.3389/fimmu.2021.766170

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Laminin Isoforms in Human Dental Pulp: Lymphatic Vessels Express Laminin-332, and Schwann Cell?Associated Laminin-211 Modulates CD163 Expression of M2-like Macrophages2021

    • Author(s)
      Yoshiba Nagako、Edanami Naoki、Ohkura Naoto、Maekawa Tomoki、Takahashi Naoki、Tsuzuno Takahiro、Maeda Takeyasu、Tabeta Koichi、Izumi Kenji、Noiri Yuichiro、Yoshiba Kunihiko
    • Journal Title

      ImmunoHorizons

      Volume: 5 Issue: 12 Pages: 1008-1020

    • DOI

      10.4049/immunohorizons.2100110

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rice peptide with amino acid substitution inhibits biofilm formation by Porphyromonas gingivalis and Fusobacterium nucleatum2021

    • Author(s)
      Matsugishi Aoi、Aoki-Nonaka Yukari、Yokoji-Takeuchi Mai、Yamada-Hara Miki、Mikami Yoshikazu、Hayatsu Manabu、Terao Yutaka、Domon Hisanori、Taniguchi Masayuki、Takahashi Naoki、Yamazaki Kazuhisa、Tabeta Koichi
    • Journal Title

      Archives of Oral Biology

      Volume: 121 Pages: 104956-104956

    • DOI

      10.1016/j.archoralbio.2020.104956

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-12020

    • Author(s)
      Maekawa Tomoki、Tamura Hikaru、Domon Hisanori、Hiyoshi Takumi、Isono Toshihito、Yonezawa Daisuke、Hayashi Naoki、Takahashi Naoki、Tabeta Koichi、Maeda Takeyasu、Oda Masataka、Ziogas Athanasios、Alexaki Vasileia Ismini、Chavakis Triantafyllos、Terao Yutaka、Hajishengallis George
    • Journal Title

      JCI Insight

      Volume: 5 Issue: 15 Pages: 136706-136706

    • DOI

      10.1172/jci.insight.136706

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epithelial TRPV1 channels: Expression, function, and pathogenicity in the oral cavity2020

    • Author(s)
      Takahashi Naoki、Tsuzuno Takahiro、Mineo Shuhei、Yamada-Hara Miki、Aoki-Nonaka Yukari、Tabeta Koichi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 62 Issue: 3 Pages: 235-241

    • DOI

      10.1016/j.job.2020.05.005

    • Related Report
      2020 Research-status 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
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp2020

    • Author(s)
      Yoshiba N.、Edanami N.、Ohkura N.、Maekawa T.、Takahashi N.、Tohma A.、Izumi K.、Maeda T.、Hosoya A.、Nakamura H.、Tabeta K.、Noiri Y.、Yoshiba K.
    • Journal Title

      Journal of Dental Research

      Volume: 99 Issue: 3 Pages: 329-338

    • DOI

      10.1177/0022034519894957

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nutritional supplements and periodontal disease prevention-Current understanding.2020

    • Author(s)
      Aoki-Nonaka Y, Matsugishi A, Lwin HY, Takahashi N, Tabeta K
    • Journal Title

      Curr Oral Health Rep

      Volume: - Issue: 2 Pages: 154-164

    • DOI

      10.1007/s40496-020-00261-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin‐dependent neutrophil lysis2019

    • Author(s)
      Hiyoshi Takumi、Domon Hisanori、Maekawa Tomoki、Nagai Kosuke、Tamura Hikaru、Takahashi Naoki、Yonezawa Daisuke、Miyoshi Tomohiro、Yoshida Akihiro、Tabeta Koichi、Terao Yutaka
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 3-4 Pages: 100-110

    • DOI

      10.1111/1348-0421.12672

    • NAID

      40021899825

    • Related Report
      2019 Research-status 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 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gingival epithelial barrier: regulation by beneficial and harmful microbes2019

    • Author(s)
      Takahashi Naoki、Sulijaya Benso、Yamada-Hara Miki、Tsuzuno Takahiro、Tabeta Koichi、Yamazaki Kazuhisa
    • Journal Title

      Tissue Barriers

      Volume: 7 Issue: 3 Pages: e1651158-e1651158

    • DOI

      10.1080/21688370.2019.1651158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Host modulation therapy using anti-inflammatory and antioxidant agents in periodontitis: A review to a clinical translation2019

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

      Archives of Oral Biology

      Volume: 105 Pages: 72-80

    • DOI

      10.1016/j.archoralbio.2019.07.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The AmyI‐1‐18 peptide derived from rice inhibits alveolar bone resorption via suppression of inflammatory cytokine production induced by lipopolysaccharide and interleukin‐1β in mice2019

    • Author(s)
      Aoki‐Nonaka Yukari、Tabeta Koichi、Yokoji Mai、Matsugishi Aoi、Matsuda Yumi、Takahashi Naoki、Sulijaya Benso、Domon Hisanori、Terao Yutaka、Taniguchi Masayuki、Yamazaki Kazuhisa
    • Journal Title

      Journal of Periodontology

      Volume: . Issue: 10 Pages: 1160-1169

    • DOI

      10.1002/jper.18-0630

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [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 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Experimental animal model in periodontal research2021

    • Author(s)
      Takahashi N
    • Organizer
      15th International Dental Collaboration of the Mekong River Region (IDCMR) Pre-conference workshops
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Antioxidant effect of food-derived peptide in human gingival epithelial cells2021

    • Author(s)
      Mineo S, Takahashi N, Tsuzuno T, Aoki-Nonaka Y, Tabeta K
    • Organizer
      99th General Session of the IADR
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒト歯肉上皮細胞における米糠由来ペプチドによる抗酸化作用の検証2021

    • Author(s)
      峯尾修平,高橋直紀,都野隆博,野中由香莉,多部田康一
    • Organizer
      第64回春季日本歯周病学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 超音波スケーラーから発生するエアロゾル特性と口腔内外吸引装置による拡散防止効果①-感水試験紙を用いた飛散方向および距離の検討-2021

    • Author(s)
      峯尾修平,高橋直紀,多部田康一
    • Organizer
      第64回秋季日本歯周病学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 超音波スケーラーから発生するエアロゾル特性と口腔内外吸引装置の拡散防止効果②-小粒径エアロゾルの粒径分布とその吸引効果の検討-2021

    • Author(s)
      高橋直紀,峯尾修平,多部田康一
    • Organizer
      第64回秋季日本歯周病学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 歯肉上皮細胞に発現するTRPV1活性化による抗炎症性作用の解析2020

    • Author(s)
      都野隆博,高橋直紀,峯尾修平,原 実生,野中由香莉,多部田康一
    • Organizer
      日本歯科保存学会2020年度春季学術大会(第152回)
    • Related Report
      2020 Research-status Report
  • [Presentation] 腸内細菌叢の変動を介した歯周病のNAFLDへの影響2020

    • 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,坪井裕理,菊池 淳,加藤 完,大野博司,山崎和久
    • Organizer
      第24回腸内細菌学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 歯肉上皮細胞における抗酸化ストレス応答を活性化させる食物由来ペプチドの探索2020

    • Author(s)
      峯尾修平,高橋直紀,都野隆博,野中由香莉,田村 光,多部田康一
    • Organizer
      日本歯科保存学会2020年度春季学術大会(第152回)
    • Related Report
      2020 Research-status Report
  • [Presentation] Porphyromonas gingivalis経口投与は腸内細菌の変化を介してNAFLD病態に影響を与える2020

    • 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
      令和2年新潟歯学会第2回例会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト歯肉上皮細胞における抗酸化ストレス応答を増強する食物由来ペプチドの探索2020

    • Author(s)
      峯尾修平,高橋直紀,都野隆博,野中由香莉,多部田康一
    • Organizer
      令和2年度新潟歯学会第2回例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Porphyromonas gingivalis aggravates experimental induced colitis in mice.2020

    • Author(s)
      Tsuzuno T, Takahashi N, Yamada-Hara M, Yokoji-Takeuchi M, Aoki-Nonaka Y, Matsugishi A, Tabeta K, Yamazaki K
    • Organizer
      Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gingival epithelial cells: a possible target for host modulation therapy?2020

    • Author(s)
      Takahashi N
    • Organizer
      Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Oral administration of Porphyromonas gingivalis aggravates intestinal inflammation in mice.2019

    • Author(s)
      Tsuzuno T, Takahashi N, Yokoji M, Yamada-Hara M, Nakajima M, Tabeta K, Yamazaki K
    • Organizer
      97th General Session of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dysbiosis of gut microbiome in Japanese patients with periodontitis.2019

    • Author(s)
      Yamazaki K, Sato K, Nakajima T, Muyazawa H, Takahashi N, Yamada-Hara M, Yokoji M, Yamazaki K
    • Organizer
      7th General Session of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [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 Research-status Report
  • [Presentation] Porphyromonas gingivalisが腸管上皮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
    • Related Report
      2019 Research-status 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 Research-status Report
  • [Presentation] Neuronal TRPV1 activation prevents alveolar bone resorption via CGRP.2019

    • Author(s)
      Takahashi N
    • Organizer
      97th General Session of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 臨床歯周病学 第3版2020

    • Author(s)
      高橋直紀,多部田康一
    • Total Pages
      5
    • Publisher
      医歯薬出版
    • ISBN
      9784263458440
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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