16S rRNA gene sequencing and LC-MS-based metabolomics show that ischemic stroke is related to gut microbiota and metabolome in rats

Background: Ischemic stroke (IS) is a common type of stroke with high rates of morbidity, mortality, and disability. Despite accumulating evidence that the gut microbiome and metabolome are associated with human diseases, whether they contribute to the pathophysiological mechanism of IS and whether microbial communities affect metabolic phenotype and function are unclear. ResultsIn this study, we integrated 16S rRNA gene sequencing and LC-MS-based metabolomics to explore the roles and underlying mechanisms of the gut microbiome and metabolome in a rat model of IS. Microbiota composition and diversity in IS and control rats were significantly different at the phylum and genus levels. The relative abundance of the phylum Firmicutes was significantly decreased, whereas Proteobacteria and Deferribacteres were markedly increased in IS rats compared with abundance levels in controls. In addition, the metabolic profiles of IS rats were significantly different from those of control rats. We detected 308 significantly dysregulated metabolites, including 155 up-regulated and 153 down-regulated, that best distinguished the IS and control groups. Furthermore, correlation analysis revealed that dysbiosis of the gut microbiota was strongly correlated with dysregulated metabolites. Overall, our results showed that IS is characterized by significant alterations in gut microbiota composition and diversity as well as metabolic phenotype. ConclusionThese results demonstrate that dysbiosis of gut microbiota and perturbations of gut microflora-related metabolites are involved in the development of IS and may serve as potential biomarkers of ischemic stroke.