Association Between cnm-Positive Streptococci and Cerebral Small Vessel Disease: Insights From Oral Health and Microbiome Status

INTRODUCTION AND AIMS: Cerebral small vessel disease (CSVD) is associated with various severe neurological outcomes; while oral cnm-positive streptococci are suggested to be involved in cerebrovascular lesions, the specific associative features between these bacteria and CSVD have not yet been systematically investigated. This study aims to investigate the prevalence of cnm-positive streptococci in patients with CSVD and explore the correlation between infection and CSVD severity. By integrating oral health indices and microbiome sequencing, we evaluate the oral hygiene status and microbial dysbiosis characteristics of cnm-positive streptococci carriers. Furthermore, cnm-positive streptococci derived from CSVD patients will be isolated, identified, and subjected to whole-genome sequencing to provide a foundation for future research. METHODS: To explore cnm-positive streptococci prevalence and its association with CSVD, we conducted a case-control study comparing their oral detection rates between healthy controls and CSVD patients. We also performed 16S rRNA gene high-throughput sequencing of oral plaque microbiota and assessed oral health, including the simplified oral hygiene index (OHI-S), the decayed, missing, and filled teeth (DMFT) index, oral hygiene practices, gingival status, and saliva scores. RESULTS: cnm-positive streptococci were more prevalent in CSVD patients, correlating with higher OHI-S and microbial dysbiosis. Multivariable regression models (adjusted for demographic/vascular risk factors) linked cnm positivity to periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), Fazekas score, and total CSVD burden (not cerebral microbleeds (CMBs)/lacunes). CONCLUSION: Oral cnm-positive streptococci are independently associated with CSVD phenotypes, particularly those characterized by white matter injury. These findings presents a potential oral-cerebrovascular interaction and imply that managing specific virulent oral strains may be a noteworthy consideration in future clinical research.