Crosstalk between oral and systemic responses

• Project/Area Number: 19K22702
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Azuma Miyuki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (90255654)
• Co-Investigator(Kenkyū-buntansha): 平山 和宏 東京大学, 大学院農学生命科学研究科(農学部), 教授 (60208858) ; 竹内 康雄 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (60396968)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腸内細菌 / 歯周細菌 / 腸管免疫 / 口腔免疫 / 歯周病原細菌 / 免疫 / 歯周病 / 細菌叢 / 腸疾患

Outline of Research at the Start

歯周プラーク細菌叢が腸内細菌および腸菅免疫に与える影響を調べるために、無菌マウスにヒト正常腸内細菌叢を移植したヒトフローラマウス(HFマウス）を作出する。HFマウスの口腔および腸管・全身の基準となる免疫応答を確認しておく。 HFマウスで、デキストラン硫酸ナトリウム (DSS)誘導性腸炎を惹起させる。その際、歯周フローラのディスバイオーシスが生じている歯周病患者の短期培養歯周細菌を口腔内投与し、腸炎発症への影響および全身および腸管免疫に与える影響を調べる。

Outline of Final Research Achievements

We found the dysbiosis occured in periodontal plaques between healthy donors and patients with severe periondontitis by microbiome analyses. We successfully performed anaerobic 10 Frequently-detectable severe periodontitis bacteria (FSPB) culture. Development of dextran sulfate sodium-induced colitis, which mimic human ulcerative colitis, were differ in three mouse breeder companies. This differences were related to intestinal microbiome and immune responses. We will plan to analyze the effects of 10FSPB treatment by oral feeding or gingival application.

Academic Significance and Societal Importance of the Research Achievements

残念ながら、最終結果の獲得には至らなかったが、樹立したマウス実験モデルで、歯周病細菌と全身疾患との関連を模倣することができれば、今後の口腔と全身とのクローストーク解析に新規のアプローチを生み出すことになる。

Research Products

• [Journal Article] Overexpression of PD‐L1 in gingival basal keratinocytes reduces periodontal inflammation in a ligature‐induced periodontitis model (2021)
  • Author(s): Wongtim Keeratika、Ikeda Eri、Ohno Tatsukuni、Nagai Shigenori、Okuhara Shigeru、Kure Keitetsu、Azuma Miyuki
  • Journal Title: Journal of Periodontology Volume: 93 Issue: 1 Pages: 146-155
  • DOI: 10.1002/jper.21-0017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japanese subgingival microbiota in health vs disease and their roles in predicted functions associated with periodontitis (2019)
  • Author(s): Ikeda E, Shiba T, Ikeda Y, Suda W, Nakasato A, Takeuchi Y, Azuma M, Hattori M, Izumi Y.
  • Journal Title: Odontology Volume: 108 Issue: 2 Pages: 280-291
  • DOI: 10.1007/s10266-019-00452-4
  • Peer Reviewed / Open Access
• [Journal Article] Deep sequencing reveals specific bacterial signatures in the subgingival microbiota of healthy subjects (2019)
  • Author(s): Ikeda Eri、Shiba Takahiko、Ikeda Yuichi、Suda Wataru、Nakasato Akinori、Takeuchi Yasuo、Azuma Miyuki、Hattori Masahira、Izumi Yuichi
  • Journal Title: Clinical Oral Investigations Volume: 23 Issue: 3 Pages: 1489-1493
  • DOI: 10.1007/s00784-019-02805-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Overexpression of immune checkpoint molecule PD-L1 in gingival basal keratinocytes regulates periodontal inflammation (2022)
  • Author(s): Keeratika Wongtim1, 2, Pornpan Piboonratanakij, Eri Ikeda, Shigeru Okuhara, Shigenori Nagai, Miyuki Azuma
  • Organizer: 2022 AIDR (International Association for Dental Research)/APR
  • Int'l Joint Research
• [Presentation] 免疫チェックポイント分子PD-L1の歯肉過剰発現は、早期および慢性の歯肉炎症を抑制する. (2020)
  • Author(s): Wongtim Keeratika, 池田 恵莉、大野 建州、永井 重徳、奥原 滋、呉 圭哲、東 みゆき.
  • Organizer: 第74回日本口腔科学会