Abstract WMP108: Brain-Oral Axis: Cnm -Positive S. mutans Infection is a Novel Risk Factor for Cerebral Bleeding

Abstract

Introduction: We previously reported that oral Streptococcus mutans expressing a collagen binding protein Cnm was associated with deep cerebral microbleeds (CMBs) and intracranial hemorrhage (ICH). Approximately 20% of S. mutans strains have the cnm gene, raising the risk of cerebral bleeding. However, the positive correlation between cnm -positive S. mutans and CMBs has been shown only in cross-sectional studies and long-term effects of cnm -positive S. mutans still remain unknown. Purpose: To determine whether cnm -positive S. mutans facilitates cerebral bleeding. Methods: In our retrospective longitudinal study, 92 stroke survivors who underwent serial 3.0 T-MRI scans at intervals of more than 6 months and received analysis of oral bacteria were consecutively enrolled. Patients without oral harboring S. mutans were excluded. The cnm gene in S. mutans isolated from dental plaque was screened using PCR techniques. CMBs were illustrated by MRI T2*-weighted GRE method (TR 550 ms, TE 12 ms, flip angle 20°, slice thickness 4.0 mm). CMBs were classified into the deep, lobar, and subtentorial CMBs. After evaluation of serial MRI scans, the number of newly evoked CMBs per 6 months was compared between cnm -positive S. mutans group ( cnm+ group) and cnm -negative S. mutans group ( cnm - group). Results: Twenty-two patients were enrolled in the cnm+ group and 70 in the cnm - group (mean age±SE 69.7±2.8 vs. 69.2±1.5 p=0.56). The two groups were not different in the mean observational period (1.37±0.13 vs. 1.46±0.08 years p=0.84) or in the prevalence of vascular risk factors, including hypertension. Total and deep CMBs significantly increased in number in the cnm + group compared to the cnm - group (mean±SD per 6 months, 0.88±1.30 vs. 0.16±0.45 for total CMBs, p=0.01; 0.47±0.80 vs. 0.03±0.15 for deep CMBs, p=0.003), while lobar and subtentorial CMBs did not increase significantly (0.22±0.50 vs. 0.07±0.32 for lobar CMBs, p=0.10; 0.19±0.61 vs. 0.06±0.17 for subtentorial CMBs, p=0.24). Two (9.1%) in the cnm + group but only one (1.6%) in the cnm - group had symptomatic cerebral hemorrhage during the observational period. Conclusions: Oral cnm -positive S. mutans facilitated formation of CMBs. Brain-oral axis may be a novel therapeutic target for cerebral bleeding.