Systemic Characterization of the Gut Microbiota Profile after Single Mild Ischemic Stroke and Recurrent Stroke in Mice

Abstract

It has been estimated that one in four stroke patients may have recurrent stroke within five years after they experienced the first stroke. Furthermore, clinical studies have shown that recurrent stroke negatively affects patient outcomes; the risk of disability and the death rate increase with each recurrent stroke. Therefore, it is urgent to find effective methods to prevent recurrent stroke. The gut microbiota has been proven to play an essential role after ischemic stroke, while sudden ischemia disrupts microbial dysbiosis, and the metabolites secreted by the microbiota also reshape the gut microenvironment. In the present study, we established a recurrent ischemic mouse model. Using this experimental model, we compared the survival rate and ischemic infarction between single MCAO and recurrent MCAO, showing that, when two surgeries were performed, the mouse survival rate dramatically decreased, while the infarction size increased. Fecal samples were collected on day 1, day 3 and day 7 after the first MCAO and day 9 (2 days after the second MCAO) for 16S sequencing, which provided a relatively comprehensive picture of the microbiota changes. By further analyzing the potential metabolic pathways, our data also highlighted several important pathways that were significantly altered after the first and recurrent stroke. In the present study, using an experimental mouse model, we showed that acute ischemic stroke, especially recurrent ischemia, significantly decreased the diversity of the gut microbiota.