Oral Carriage of <i>Streptococcus mutans</i> Harboring the <i>cnm</i> Gene Relates to an Increased Incidence of Cerebral Microbleeds.

Abstract

Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with <i>Streptococcus mutans</i> expressing Cnm, a collagen-binding protein in the oral cavity. <i>S.</i><i>mutans</i> is a major pathogen responsible for dental caries. Repeated challenge with <i>S.</i><i>mutans</i> harboring the <i>cnm</i> gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of <i>cnm</i>-positive <i>S.</i><i>mutans</i> to the development of CMB. 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 <i>cnm</i>-positive <i>S.</i><i>mutans</i> were compared with those without. Quasi-Poisson regression models were used to explore associations between <i>cnm</i>-positive <i>S.</i><i>mutans</i> and the increase in number of CMB between the 2 magnetic resonance imaging scans. A total of 111 patients were identified; 21 (19%) with <i>cnm</i>-positive <i>S.</i><i>mutans</i> 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 <i>cnm</i>-positive <i>S.</i><i>mutans</i> (52% versus 23%; <i>P</i>=0.008). The incidence of CMB was significantly higher in the group with <i>cnm</i>-positive <i>S.</i><i>mutans</i>, 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). This study demonstrates that <i>cnm</i>-positive <i>S.</i><i>mutans</i> is associated with an increased incidence of CMB. Treatment for <i>cnm</i>-positive <i>S.</i><i>mutans</i> infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.