The establishment of periodontal treatment by strengthening gingival epithelial barrier using a functional metabolite

• Project/Area Number: 17H06701
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Periodontology
• Research Institution: Niigata University
• Principal Investigator: Matsukawa Yumi 新潟大学, 医歯学総合病院, 医員 (30804554)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 歯周病 / 機能性脂肪酸 / 上皮バリア / 歯周炎 / 上皮バリア機能 / 不飽和脂肪酸

Outline of Final Research Achievements

10-Hydroxy-cis-12-octadecenoic acid (HYA), a bioactive metabolite generated by probiotic microorganisms during the process of fatty acid metabolism, has been studied for its protective effects against epithelial barrier impairment in the intestines.
We found that HYA significantly inhibited barrier impairment induced by Porphyromonas gingivalis, a representative periodontopathic bacterium. The degradation of E-cadherin and beta-catenin, basic components of the epithelial barrier, was prevented in vitro. Oral inoculation of HYA in a mouse experimental periodontitis model suppressed the bacteria-induced degradation of E-cadherin and subsequent inflammatory cytokine production in the gingival tissue.
Collectively, these results suggest that HYA exerts a protective function against periodontopathic bacteria-induced gingival epithelial barrier impairment and contributes to the suppression of inflammatory responses in periodontal diseases.

Academic Significance and Societal Importance of the Research Achievements

近年のメタボローム解析技術の発展により、宿主に対して生理活性を有する機能性代謝産物の存在が相次いで明らかとなっているが、歯科分野における機能解析および臨床応用に関する報告は本研究が初めてであり、学術的意義が大きい。
また、本研究は、機能性脂肪酸を用いた歯肉上皮バリア機能強化をターゲットとした新たな歯周病予防法の可能性を示した。最近の抗菌薬耐性菌の問題を鑑みると、細菌側に働きかけるのではなく、細菌に強い組織にする、すなわち上皮バリア機能を強化することによる歯周病予防法開発の社会的意義は大きい。

Research Products

• [Journal Article] A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Resveratrol suppresses the alveolar bone resorption induced by artificial trauma from occlusion in mice (2017)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A Bioactive Metabolite Prevents P. gingivalis-Induced Gingival Epithelial Barrier Disruption (2019)
  • Author(s): Yamada-Hara M, Takahashi N, Matsuda-Matsukawa Y, Sato K, Yokoji-Takeuchi M, Sulijaya B, Tabeta K, Yamazaki K
  • Organizer: International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment, Phuket, Thailand
  • Int'l Joint Research
• [Presentation] Preventive Effect of Microbial Metabolite on Periodontitis in Mice (2018)
  • 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, London
  • Int'l Joint Research
• [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、松田由実、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
• [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, Ohno H
  • Organizer: Pg Melbourne, Melbourne
  • Int'l Joint Research
• [Presentation] Beneficial 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: The 65th Annual Meeting of the JADR
  • Int'l Joint Research
• [Presentation] 米由来抗菌ペプチドの歯周炎モデルマウスにおける抗炎症作用の検討 (2017)
  • Author(s): 野中由香莉，多部田康一，横地麻衣，松田由実，山崎和久，吉江弘正
  • Organizer: 第60回春季日本歯周病学会学術大会
• [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 日本歯科保存学会秋季学術大会