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

Stroke. 2020 Dec;51(12):3632-3639. doi: 10.1161/STROKEAHA.120.029607. Epub 2020 Nov 5.

Abstract

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.

Keywords: Streptococcus mutans; blood pressure; dental caries; hemorrhage; risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics*
  • Aged
  • Aged, 80 and over
  • Carrier Proteins / genetics*
  • Carrier State / epidemiology*
  • Carrier State / microbiology
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology*
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / epidemiology*
  • Female
  • Humans
  • Incidence
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mouth / microbiology
  • Retrospective Studies
  • Streptococcal Infections / epidemiology*
  • Streptococcal Infections / microbiology
  • Streptococcus mutans / genetics*
  • Stroke, Lacunar / diagnostic imaging
  • White Matter / diagnostic imaging

Substances

  • Adhesins, Bacterial
  • Carrier Proteins
  • Cnm protein, Streptococcus mutans