Microbiota in cerebrovascular disease: A key player and future therapeutic target

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.