Establishment and development of metagenomics-based priodontitis diagnostic platform

• Project/Area Number: 17K19747
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Oral Science and related fields
• Research Institution: Niigata University
• Principal Investigator: Maekawa Tomoki 新潟大学, 医歯学系, 研究准教授 (50625168)
• Co-Investigator(Kenkyū-buntansha): 奥田 修二郎 新潟大学, 医歯学系, 准教授 (00512310) ; 土門 久哲 新潟大学, 医歯学系, 助教 (00594350) ; 寺尾 豊 新潟大学, 医歯学系, 教授 (50397717) ; 米澤 大輔 新潟大学, 医歯学系, 助教 (90711896)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 歯周病治療 / デジタルプラットフォーム / 歯周炎 / クリティカルパス / ディープラーニング / メタゲノム解析 / 菌叢解析 / 精密医療 / Keystone細菌 / 歯周病 / 歯周病治療学 / 歯周治療学

Outline of Final Research Achievements

We first conduct that classified of human periodontitis patients as invasive periodontitis, periodontitis with gingival abscess, chronic periodontitis. Then, a total of 57 subgingival plaque samples from normal periodontal patients with normal bacterial composition balance were collected.The collected samples were prepared for metagenome analysis, and metagenomic analysis of all bacteria was performed by the next-generation sequencer. P. g was found to cause periodontitis by reducing immune function. A similar approach is being performed on bacteria that are central to newly identified diseases.

Academic Significance and Societal Importance of the Research Achievements

歯周炎が細菌感染によって引き起こされることが明らかでありながらも，細菌学の観点に立ったアプローチはこれまでに例が少ない．そのために，歯周炎には全て同様な物理的，もしくは化学的にプラークを除去する治療法しか存在せず，経験に頼った旧時代的な診療になりがちであった．本研究成果によって，歯周炎だけでなく他の混合感染症の成り立ちを理解するための，新たなアプローチ法に展開することが可能となる．さらに，歯周ポケットの細菌検査が，歯周炎の「進行程度」を示す新しい歯周炎の検査項目の開発にもなり得る．

Research Products

• [Int'l Joint Research] ペンシルベニア大学(米国)
• [Int'l Joint Research] ドレスデン工科大学(ドイツ)
• [Int'l Joint Research] チュラロンコン大学(タイ)
• [Int'l Joint Research] マニラ中央大学(フィリピン)
• [Journal Article] Complement-Dependent Mechanisms and Interventions in Periodontal Disease (2019)
  • Author(s): Hajishengallis G, Kajikawa T, Hajishengallis E, Maekawa T, Reis ES, Mastellos DC, Yancopoulou D, Hasturk H, Lambris JD.
  • Journal Title: Frontiers in Immunology Volume: 10
  • DOI: 10.3389/fimmu.2019.00406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin‐dependent neutrophil lysis (2019)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Peptides from rice endosperm protein restrain periodontal bone loss in mouse model of periodontitis (2019)
  • Author(s): Tamura Hikaru、Maekawa Tomoki、Domon Hisanori、Hiyoshi Takumi、Yonezawa Daisuke、Nagai Kosuke、Ochiai Akihito、Taniguchi Masayuki、Tabeta Koichi、Maeda Takeyasu、Terao Yutaka
  • Journal Title: Archives of Oral Biology Volume: 98 Pages: 132-139
  • DOI: 10.1016/j.archoralbio.2018.11.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunization with pneumococcal elongation factor Tu enhances serotype-independent protection against Streptococcus pneumoniae infection (2019)
  • Author(s): Nagai Kosuke、Domon Hisanori、Maekawa Tomoki、Hiyoshi Takumi、Tamura Hikaru、Yonezawa Daisuke、Habuka Rie、Saitoh Akihiko、Terao Yutaka
  • Journal Title: Vaccine Volume: 37 Issue: 1 Pages: 160-168
  • DOI: 10.1016/j.vaccine.2018.11.015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children with acute otitis media in Japan from 2014 to 2017 (2019)
  • Author(s): Nagai Kosuke、Kimura Osamu、Domon Hisanori、Maekawa Tomoki、Yonezawa Daisuke、Terao Yutaka
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Issue: 3 Pages: 229-232
  • DOI: 10.1016/j.jiac.2018.08.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniae (2018)
  • Author(s): Domon Hisanori、Maekawa Tomoki、Yonezawa Daisuke、Nagai Kosuke、Oda Masataka、Yanagihara Katsunori、Terao Yutaka
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 62 Issue: 11
  • DOI: 10.1128/aac.00161-18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis (2018)
  • Author(s): Bostanci N, Bao K, Li X, Maekawa T, Grossmann J, Panse C, Briones RA, Resuello RRG, Tuplano JV, Garcia CAG, Reis ES, Lambris JD, Hajishengallis G
  • Journal Title: Journal of Proteome Research Volume: 17 Issue: 9 Pages: 3153-3175
  • DOI: 10.1021/acs.jproteome.8b00263
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-like Receptors and Cytokines in Pneumococcal Pneumonia (2018)
  • Author(s): Domon Hisanori、Nagai Kosuke、Maekawa Tomoki、Oda Masataka、Yonezawa Daisuke、Takeda Wataru、Hiyoshi Takumi、Tamura Hikaru、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Front Immunol Volume: 印刷中 Pages: 732-732
  • DOI: 10.3389/fimmu.2018.00732
  • Peer Reviewed / Open Access
• [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] Sulfated vizantin induces the formation of macrophage extracellular traps (2018)
  • Author(s): Oda Masataka、Kurosawa Mie、Yamamoto Hirofumi、Domon Hisanori、Kimura Tatsuya、Isono Toshihito、Maekawa Tomoki、Hayashi Naoki、Yamada Noriteru、Furue Yui、Kai Daichi、Terao Yutaka
  • Journal Title: Microbiol Immunol Volume: 印刷中 Issue: 5 Pages: 0-0
  • DOI: 10.1111/1348-0421.12589
  • NAID: 40021560445
  • Peer Reviewed / Open Access
• [Journal Article] Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4 (2018)
  • Author(s): Nagai Kosuke、Domon Hisanori、Maekawa Tomoki、Oda Masataka、Hiyoshi Takumi、Tamura Hikaru、Yonezawa Daisuke、Arai Yoshiaki、Yokoji Mai、Tabeta Koichi、Habuka Rie、Saitoh Akihiko、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Cell Immunol Volume: 325 Pages: 14-22
  • DOI: 10.1016/j.cellimm.2018.01.006
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche. (2017)
  • Author(s): Mitroulis I, Chen LS, Singh RP, Kourtzelis I, Economopoulou M, Kajikawa T, Troullinaki M, Ziogas A, Ruppova K, Hosur K, Maekawa T, Wang B, Subramanian P, Tonn T, Verginis P, von Bonin M, Wobus M, Bornh M, Grinenko T, Di Scala M, Hidalgo A, Wielockx B, Hajishengallis G, Chavakis T.
  • Journal Title: J Clin Invest. Volume: 127 Issue: 10 Pages: 3624-3639
  • DOI: 10.1172/jci92571
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice (2017)
  • Author(s): Oda Masataka、Domon Hisanori、Kurosawa Mie、Isono Toshihito、Maekawa Tomoki、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Front Cell Infect Microbiol Volume: 7 Pages: 300-300
  • DOI: 10.3389/fcimb.2017.00300
  • Peer Reviewed / Open Access
• [Presentation] Genetic and Intervention Studies Implicating Keystone Pathogens and Del-1 as Major Targets for the Treatment of Periodontitis (2019)
  • Author(s): Maekawa T
  • Organizer: International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment, Phuket, Thailand
  • Int'l Joint Research / Invited
• [Presentation] Del-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in periodontitis, rheumatoid arthritis and pneumonia of non-human primates (2019)
  • Author(s): Maekawa T
  • Organizer: 6th Symposium of the Smart-Aging Research Center, Tohoku University
  • Invited
• [Presentation] 内因性抗炎症分子Del-1を介したマクロライド系抗菌薬の新作用機序 (2019)
  • Author(s): 前川知樹
  • Organizer: 第4回日本骨免疫学会ウインターセミナー，軽井沢
• [Presentation] 内因性抗炎症Del-1分子による炎症性骨破壊―歯周病とリウマチ―の治療戦略 (2018)
  • Author(s): 前川知樹
  • Organizer: 第60回歯科基礎医学会学術大会，福岡
• [Presentation] Del-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in periodontitis (2018)
  • Author(s): Maekawa T
  • Organizer: Niigata U-CU Seminar in Periodontal Research. Chulalongkorn University, Bangkok, Thailand
  • Int'l Joint Research
• [Presentation] Local regulator Del1 inhibits bone-resorption via suppression of Wnt5a-Ror2 signaling (2018)
  • Author(s): Maekawa T, Domon H, Kobayashi Y, Nagai K, Yonezawa D, Terao Y, Maeda T, Hajishengallis G
  • Organizer: 96th General Session & Exhibition of the IADR, London, England
  • Int'l Joint Research
• [Presentation] Local regulator Del1 inhibits bone-resorption via suppression of Wnt5a-Ror2 signaling axis (2018)
  • Author(s): Maekawa T, Kobayashi Y, Domon H, Tamura H, Hiyoshi T, Maeda T, Terao Y, Hajishengallis G
  • Organizer: ASBMR 2018 Annual Meeting, Montreal, Canada
  • Int'l Joint Research
• [Presentation] 内因性抗炎症分子Del-1分子誘導による炎症性骨破壊の新規治療戦略 (2018)
  • Author(s): 前川知樹，小林泰浩，土門久哲，田村 光，日吉 巧，永井康介，寺尾 豊，前田健康
  • Organizer: 第４回日本骨免疫学会，沖縄
• [Presentation] 内因性抗炎症Del-1分子誘導による炎症性骨破壊の新規治療戦略 (2018)
  • Author(s): 前川知樹
  • Organizer: 秋季日本歯周病学会学術大会，大阪
• [Presentation] 内因性抗炎症分子Del-1を介したマクロライド系抗菌薬の新作用機序 (2018)
  • Author(s): 前川知樹
  • Organizer: 第25回マクロライド新作用研究会，東京
• [Presentation] 内因性Del-1分子と歯周病．クローズアップセッション「骨免疫と歯周病」 (2018)
  • Author(s): 前川知樹
  • Organizer: 第3回日本骨免疫学会ウインターセミナー
• [Presentation] Del-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in periodontitis. (2018)
  • Author(s): Maekawa T, Maeda T
  • Organizer: International collaborative symposium on development of human resources in practical oral health and treatment
  • Int'l Joint Research
• [Presentation] Del-1分子による歯周炎の制御メカニズム解析とサルの応用研究 (2018)
  • Author(s): 前川知樹
  • Organizer: 第3回口腔医科学フロンティア研究会
• [Presentation] Inhibition of pre-existing natural periodontal inflammation in non-human primates by a locally administered peptide inhibitor of complement C3. (2017)
  • Author(s): Maekawa Tomoki
  • Organizer: 7th TIMNAS and 4th JSMiD 2017
  • Int'l Joint Research / Invited
• [Presentation] Genetic and intervention studies implicating keystone pathogens as a major target for the treatment of periodontitis. (2017)
  • Author(s): Maekawa Tomoki
  • Organizer: The 65th Annual Meeting of Japanese Association for Dental Research
  • Int'l Joint Research
• [Presentation] 内因性Del-1分子による炎症性骨吸収の制御メカニズム解析とサルの応用研究 (2017)
  • Author(s): 前川知樹
  • Organizer: 第60回春季日本歯周病学会学術大会
• [Presentation] Del-1分子による歯周炎制御メカニズム解析とサルの応用研究 (2017)
  • Author(s): 前川知樹
  • Organizer: 第59回歯科基礎医学会学術大会・総会
• [Presentation] 抗炎症性分子Del-1はWnt5a-Ror2伝達経路を阻害し骨吸収を抑制する (2017)
  • Author(s): 前川知樹
  • Organizer: 第3回日本骨免疫学会
• [Presentation] 抗炎症性分子Del-1はWnt5a-Ror2伝達経路を阻害し骨吸収を抑制する (2017)
  • Author(s): 前川知樹
  • Organizer: 第59回歯科基礎医学会学術大会・総会
• [Presentation] 肺炎の重症化に伴い誘導される宿主由来エラスターゼの病原性解析 (2017)
  • Author(s): 土門久哲，前川知樹，永井康介，山口雅也，川端重忠，寺尾 豊
  • Organizer: 第59回歯科基礎医学会学術大会・総会
• [Presentation] 自己溶菌に伴い放出される肺炎球菌の菌体内病原因子の同定と分子解析 (2017)
  • Author(s): 永井康介，土門久哲，前川知樹，山口雅也，川端重忠，寺尾 豊
  • Organizer: 第59回歯科基礎医学会学術大会・総会
• [Remarks] 新潟大学大学院医歯学総合研究科 高度口腔機能教育研究センター
  • URL: http://www.caos-niigata-univ.net/