Dysbiosis Of Gut Microbiota Promotes Post-stroke Brain Injury:Clinical Correlation Analysis And Animal Studies

BackgroundIntestinal microbiota is closely related to multiple risk factors in stroke.However,the pathological effect of intestinal microbiota on acute brain injury is still unclear.Studies have reported that gut microbiota dysbiosis caused by antibiotics can lead to differentiation of intestinal inflammatory T cells,which finally affects the brain injury in mice.The early report of our study has shown that the characteristics of gut microbiota in patients with acute stroke were significantly changed,and it seems worse in patients with more severe stroke.Microbiota dysbiosis in patients with acute stroke may play an important role in acute brain injury.Purpose and significanceIn this study,we will figure out the role of the microbiota dysbiosis in acute stroke patients on brain injury.We hypothesis that the dysbiotic microbiota occurred in stroke patients was a new risk factor for stroke with a novel microbiota-dependent model for stroke was built up for assessing the microbiota dysbiosis in patients.Study of microbiota may provide a new treatment strategy targeting intestinal microbiota for stroke.MethodA 194-member cohort including 104 acute stroke patients and 90 individuals was established for building a novel microbiota-dependent model,called as Microbial index of Stroke(MIS)for assessing the microbiota dysbiosis in stroke patients.Correlation between the microbiota dysbiosis and the severity of brain injury in patients was further investigated.Next fecal microbiota transplantation was implemented to determine the effect of microbiota dysbiosis in patients with different MIS on acute brain injury in C57BL/6 mice.The fecal recipient mice were subjected to 60 minutes' middle cerebral artery occlusion.Infarct volume was measured by TTC staining.At the end point,tissues were preserved for immunologic investigations using flow cytometry.ResultsThe microbiota-dependent model of Stroke(MIS)was established with eighteen bacteria which were the most differentially abundant taxa between patients and controls.Area under the curve(AUC)of receiver operating characteristic curve(ROC)for assessing the effectiveness of the MIS for distinguishing the stroke patients from controls was 74.9%.Correlation of the microbial index and the scores of NIHSS was obviously significantly positive in patients with anterior circulation ischemic stroke.We found that brain injury after the middle cerebral artery occlusion(MCAO)was more significantly developed in high-index fecal recipient mice as compared to the low-index fecal recipient mice.Moreover,the high-index mice have IL-17+?? T cells increased and regulatory T cells decreased after MCAO surgery with accelerated brain injury compared to low-index mice.ConclusionThe Microbial index of Stroke(MIS)model may be a useful tool for assessingthe microbiota disturbance in stroke patients from which the intestinal microbiota disordered differently in patients and it was positively correlated with the severity of brain injury in patients with anterior circulation ischemic stroke.Results of the fecal microbiota transplantation experiments declared that the more severe disturbance of the microbiota resulted in much more brain damage and worse neurological severity scores in the fecal recipient MCAO mice.Flow cytometry results showed that higher disturbance of the microbiota led to increased IL-17+?? T cells and decreased Treg cells in spleens of the fecal recipient MCAO mice.