Abstract
BACKGROUND: Stroke, a leading cause of disability worldwide, has been associated with periodontitis. However, whether stroke risk is related to oral microbiota remains unknown. This study aims to evaluate the associations between the oral microbiome and ischemic stroke risk. METHODS: In a case-control study of 134 case-control pairs nested within a prospective cohort study, we examined pre-diagnostic oral microbiome in association with stroke risk via shotgun metagenomic sequencing. The microbial sub-community and functional profiling were performed using Latent Dirichlet Allocation and HUMAnN2. Associations of microbial diversity, sub-community structure, and individual microbial features with ischemic stroke risk were evaluated via conditional logistic regression. RESULTS: Alpha and beta diversities differ significantly between cases and controls. One genus- and two species-level sub-communities were significantly associated with decreased ischemic stroke risk, with odds ratios (95% confidence intervals) of 0.52 (0.31-0.90), 0.51 (0.31-0.84), and 0.60 (0.36-0.99), respectively. These associations were potentially driven by the representative taxa in these sub-communities, i.e., genus Corynebacterium and Lautropia, and species Lautropia mirabilis and Neisseria elongate (p < 0.05). Additionally, 55 taxa, 1,237 gene families, and 90 metabolic pathways were associated with ischemic stroke risk at p < 0.05. CONCLUSION: Our study highlights the role of oral microbiota in the etiology of ischemic stroke and calls for further research.