Elucidation of effects of cariogenic bacteria on organ-linked network due to oral barrier breakdown

• Project/Area Number: 18H03010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Nakano Kazuhiko 大阪大学, 歯学研究科, 教授 (00379083)
• Co-Investigator(Kenkyū-buntansha): 野村 良太 大阪大学, 歯学研究科, 准教授 (90437385) ; 大川 玲奈 大阪大学, 歯学部附属病院, 講師 (80437384) ; 大継 將寿 大阪大学, 歯学研究科, 助教 (40803086) ; 鋸屋 侑布子 大阪大学, 歯学研究科, 助教 (40803078)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: Streptococcus mutans / コラーゲン結合タンパク / 感染性心内膜炎 / 脳出血 / 脳内微小出血 / IgA腎症 / 重度う蝕 / Citrus unshiu / 微小脳出血 / 血管内皮細胞 / デンタルプラーク / う蝕原性細菌 / 口腔バリア / 臓器連関 / 非アルコール性脂肪肝炎 / う蝕 / ラットモデル / 臨床検体 / 全身疾患 / 齲蝕 / 動物モデル / う蝕原生性細菌

Outline of Final Research Achievements

We evaluated the pathogenicity of 120-kDa collagen-binding proteins (CBP) of Streptococcus mutans for systemic disease development. CBP-positive S. mutans organisms in the oral cavity were found to be involved in development of cardiovascular diseases, including infective endocarditis and cerebral microbleeds, as well as IgA nephropathy, classified as a designated intractable disease. As a novel approach for inhibition of S. mutans, fruit-derived components exhibited inhibitory effects on both bacterial growth and biofilm formation activities.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、口腔内に存在するCBP 陽性のS. mutansがう蝕だけでなく様々な全身疾患の増悪化に関わることが明らかになり、口腔衛生状態を良好に保ちう蝕の予防に努めることが、全身疾患の予防にも有効である可能性を示すことができた。また、ある種の食品を応用することにより、S. mutansによるう蝕や全身疾患を低減できる可能性を示すことができた。

Research Products

• [Journal Article] Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions (2020)
  • Author(s): Shuhei Naka, Misaki T, Wato K, Ito S, Nagasawa Y, Nomura R, Otsugu M, Matsumoto-Nakano M, Nakano K, Kumagai H, Oshima N
  • Journal Title: Clinical and Experimental Nephrology Volume: 24(12) Issue: 12 Pages: 1122-1131
  • DOI: 10.1007/s10157-020-01961-1
  • Peer Reviewed / Open Access
• [Journal Article] Oral carriage of Streptococcus mutans harboring the cnm gene is related to an increased incidence of cerebral microbleeds (2020)
  • Author(s): Hosoki S, Saito S, Tonomura S, Ishiyama H, Yoshimoto T, Ikeda S, Ikenouchi H, Yamamoto Y, Hattori Y, Miwa K, Friedland RP, Carare RO, Nakahara J, Suzuki N, Koga M, Toyoda K, Nomura R, Nakano K, Takegami M, Ihara M.
  • Journal Title: Stroke Volume: 51 Issue: 12 Pages: 3632-3639
  • DOI: 10.1161/strokeaha.120.029607
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Potential involvement of Streptococcus mutans possessing collagen binding protein Cnm in infective endocarditis (2020)
  • Author(s): Nomura Ryota、Otsugu Masatoshi、Hamada Masakazu、Matayoshi Saaya、Teramoto Noboru、Iwashita Naoki、Naka Shuhei、Matsumoto-Nakano Michiyo、Nakano Kazuhiko
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 19118-19118
  • DOI: 10.1038/s41598-020-75933-6
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of severe dental caries induced by Streptococcus mutans to the pathogenicity of infective endocarditis (2020)
  • Author(s): Nomura R, Matayoshi S, Otsugu M, Kitamura T, Teramoto N, Nakano K.
  • Journal Title: Infection and Immunity Volume: - Issue: 7
  • DOI: 10.1128/iai.00897-19
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: A pilot study (2019)
  • Author(s): Tonomura S, Naka S, Tabata K, Hara T, Mori K, Tanaka S, Sumida Y, Kanemasa K, Nomura R, Matsumoto-Nakano M, Ihara M, Takahashi N, Nakano K.
  • Journal Title: BMJ Open Gastroenterology Volume: 6 Issue: 1 Pages: e000329-e000329
  • DOI: 10.1136/bmjgast-2019-000329
  • Peer Reviewed / Open Access
• [Journal Article] Specific strains of Streptococcus mutans, a pathogen of dental caries, in the tonsils, are associated with IgA nephropathy. (2019)
  • Author(s): Ito S, Misaki T, Naka S, Wato K, Nagasawa Y, Nomura R, Otsugu M, Matsumoto-Nakano M, Nakano K, Kumagai H, Oshima N.
  • Journal Title: Scientific Reports Volume: 27;9(1) Issue: 1 Pages: 20130-20130
  • DOI: 10.1038/s41598-019-56679-2
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal comparison of Streptococcus mutans-induced aggravation of non-alcoholic steatohepatitis in mice (2018)
  • Author(s): Naka Shuhei、Wato Kaoruko、Hatakeyama Rina、Okawa Rena、Nomura Ryota、Nakano Kazuhiko
  • Journal Title: Journal of Oral Microbiology Volume: 10 Issue: 1 Pages: 1428005-1428005
  • DOI: 10.1080/20002297.2018.1428005
  • Peer Reviewed / Open Access
• [Journal Article] Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients. (2018)
  • Author(s): Misaki T, Naka S, Wato K, Hatakeyama R, Nagasawa Y, Ito S, Inaba H, Nomura R, Matsumoto-Nakano M, Nakano K
  • Journal Title: Nephron Volume: Epub Issue: 2 Pages: 143-149
  • DOI: 10.1159/000487103
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein. (2018)
  • Author(s): Inenaga C, Hokamura K, Nakano K, Nomura R, Naka S, Ohashi T, Ooshima T, Kuriyama N, Hamasaki T, Wada K, Umemura K, Tanaka T
  • Journal Title: World Neurosurgery Volume: 113 Pages: 77-81
  • DOI: 10.1016/j.wneu.2018.01.158
  • Peer Reviewed / Open Access
• [Presentation] Association of breastfeeding duration with mother-to-child transmission of Streptococcus mutans with collagen-binding activity (2020)
  • Author(s): Otsugu M, Kitamura T, Nomura R, Nakano K.
  • Organizer: 67th ORCA (European Organization of Caries Research) Congress
  • Int'l Joint Research
• [Presentation] Evaluation of collagen-binding properties of sterilized Streptococcus mutans (2020)
  • Author(s): Suehiro Y, Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 68th Conference of Japanese Association of Dental Research
  • Int'l Joint Research
• [Presentation] 死菌処理したStreptococcus mutansのコラーゲン結合能の評価 (2020)
  • Author(s): 末廣雄登、又吉紗綾、大継將寿、野村良太、仲野和彦
  • Organizer: 第58回日本小児歯科学会大会
• [Presentation] 長期飼育のラット齲蝕モデルにおけるIgA腎症発症の検討 (2019)
  • Author(s): 和唐薫子、仲周平、野村良太、仲野道代、仲野和彦
  • Organizer: 第57回日本小児歯科学会
• [Presentation] Streptococcus mutans associated with severe dental caries induces infective endocarditis (2019)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第97回国際歯科学会
  • Int'l Joint Research
• [Presentation] Streptococcus mutans Infection Transiently Induces IgA Nephropathy-like Lesions in Rats (2019)
  • Author(s): Wato K, Naka S, Misaki T, Nagasawa Y, Ito S, Inaba H, Nomura R, Matsumoto-Nakano M, Nakano K.
  • Organizer: 第97回国際歯科学会
  • Int'l Joint Research
• [Presentation] Systemic evaluation of rat model of simultaneous dental caries and infective endocarditis (2019)
  • Author(s): Nomura R, Matayoshi S, Otsugu M, Kitamura T, Ooshima T, Nakano K.
  • Organizer: 第66回ヨーロッパう蝕学会
  • Int'l Joint Research
• [Presentation] Evaluation of heart conditions in rat model with severe dental caries and heart valve injury (2019)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第9回日タイ韓6大学シンポジウム
  • Int'l Joint Research
• [Presentation] 重度齲蝕によって誘発されるラット感染性心内膜炎新規モデルの構築 (2018)
  • Author(s): 又吉紗綾、大継將寿、野村良太、仲野和彦
  • Organizer: 第56回日本小児歯科学会大会
• [Presentation] Evaluation of severe dental caries induced by Streptococcus mutans during development of infective endocarditis in rats (2018)
  • Author(s): Nomura R, Otsugu M, Matayoshi S, Nakano K.
  • Organizer: 第65回ヨーロッパう蝕学会
  • Int'l Joint Research
• [Presentation] Streptococcus mutans-induced infective endocarditis in severe dental caries model rats (2018)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第66回国際歯科研究学会日本部会総会・学術大会
  • Int'l Joint Research
• [Book] 生産と技術 (2020)
  • Author(s): 野村良太、仲野和彦
  • Total Pages: 4
  • Publisher: 一般社団法人生産技術振興協会