Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

Satoshi Hosoki, Satoshi Saito, Shuichi Tonomura, Hiroyuki Ishiyama, Takeshi Yoshimoto, Shuhei Ikeda, Hajime Ikenouchi, Yumi Yamamoto, Yorito Hattori, Kaori Miwa, Robert P. Friedland, Roxana O. Carare, Jin Nakahara, Norihiro Suzuki, Masatoshi Koga, Kazunori Toyoda, Ryota Nomura, Kazuhiko Nakano, Misa Takegami, Masafumi Ihara

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background and Purpose: Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with Streptococcus mutans expressing Cnm, a collagen-binding protein in the oral cavity. S. mutans is a major pathogen responsible for dental caries. Repeated challenge with S. mutans harboring the cnm gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of cnm-positive S. mutans to the development of CMB. Methods: We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with cnm-positive S. mutans were compared with those without. Quasi-Poisson regression models were used to explore associations between cnm-positive S. mutans and the increase in number of CMB between the 2 magnetic resonance imaging scans. Results: A total of 111 patients were identified; 21 (19%) with cnm-positive S. mutans and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with cnm-positive S. mutans (52% versus 23%; P=0.008). The incidence of CMB was significantly higher in the group with cnm-positive S. mutans, especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9-13.6] for CMB in any brain region; 15.0 [5.4-42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8-11.9] for CMB in any brain region; 13.9 [4.3-44.5] for deep CMB). Conclusions: This study demonstrates that cnm-positive S. mutans is associated with an increased incidence of CMB. Treatment for cnm-positive S. mutans infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.

Original languageEnglish
Pages (from-to)3632-3639
Number of pages8
Issue number12
Publication statusPublished - 2020 Dec 1


  • Streptococcus mutans
  • blood pressure
  • dental caries
  • hemorrhage
  • risk factor

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing


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