Thrombus-associated microbiota in acute ischemic stroke patients

Background: Despite a reduction in stroke incidence and age-standardized death rates, stroke remains a leading cause of death and disability worldwide. Significant interest in recent years has focused on the microbiota-host interaction because accumulating evidence has revealed myriad ways in which bacteria may contribute to risk of stroke and adverse outcomes after stroke. The emergence of endovascular thrombectomy as a treatment provides a unique opportunity to utilize thrombus retrieved from cerebral arteries to fill knowledge gaps about the influence of bacteria on stroke pathophysiology. While bacterial signatures have been confirmed in cerebral thrombi, the exact nature of the pathogenesis has not been established. Methods: Thrombi were obtained from a cohort of adult ischemic stroke patients during standard of care thrombectomy. After DNA extraction and quantification, thrombi underwent 16S rRNA amplicon-based metagenomic sequencing, followed by bioinformatics processing. Taxonomic identification of bacterial colonies isolated on Agar plates from plated suspension was performed using DNA extraction and full length 16S Sanger sequencing. Results: A broad diversity of bacterial signatures was identified in specimens, primarily of cariogenic origin. Conclusion: In this small study, we demonstrate proof of concept and technical feasibility for amplicon-based metagenomic sequencing of arterial thrombi and briefly discuss preliminary findings, challenges, and near-term translational opportunities for thrombus genomics.

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