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.

Stroke is the second leading cause of death and a significant cause of disability worldwide. Recent advances in DNA sequencing, proteomics, metabolomics, and computational tools are dramatically increasing access to the identification of host–microbiota interactions in systemic diseases. In this review, we describe the accumulating evidence showing how human microbiota plays an essential role in cerebrovascular diseases. We introduce the symbiotic relationships between microbiota and the mucosal immune system, focusing on differences by anatomical sites. Microbiota directly or indirectly contributes to the pathogenesis of traditional vascular risk factors including age, obesity, diabetes mellitus, dyslipidemia, and hypertension. Moreover, recent studies proposed independent effects of the microbiome on the progression of various subtypes of stroke through direct microbial invasion, exotoxins, functional amyloids, inflammation, and microbe-derived metabolites. We propose the critical concept of gene-microbial interaction to elucidate the heterogeneity of stroke and provide possible therapeutic avenues. We suggest ways to resolve the vast inter-individual diversity of cerebrovascular disease and mechanisms for personalized prevention and treatment.

Background: Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host–microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD. Methods: This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD. Results: Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0–17.5) vs 20.0 (5.0–25.0), p=0.06; 5.1 (4.0–7.9) vs 4.4 (3.7–5.3), p=0.13, respectively). Conclusions: Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

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