The Value Of Gut Microbiota On The Prognosis Of Acute Ischemic Stroke

Background and objective:Gut microbiota is associated with metabolic diseases by regulating host metabolism and inflammation and participate in the occurrence and development of central nervous system diseases.At present,studies have showed the changes in gut microbiota between patients with ischemic stroke and healthy controls using the 16S rRNA method.The purpose of this study is to explore the value of gut microbiota in the prognosis of ischemic stroke by metagenomics and to explore the association between the changes of gut microbiota and the poor functional outcome so as to provide a new target for clinical treatment of ischemic stroke.Methods:The patients with acute ischemic stroke(AIS)within 72 hours of onset were continuously included from the third Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2018 to March 2019,and their stool samples were collected within 72 hours of admission.The control group was people without a history of stroke during the same period.The baseline data of included patients and control group was collected,and DNA was extracted from stool samples for sequencing on the Illumina HiSeq 2500(high-throughput sequencing)platform.The enrolled AIS patients were followed up face-to-face or by telephone 90 days after the onset,with poor functional outcome(mRS score>2 points)as the endpoint.IBM SPSS software version 24.0 and R software(version 3.5.0)was used for statistical analysis of the data,P<0.05(two-sided)was considered statistically significant.Wiloxon rank-sum and LEfSe methods were used to screen different species.Gene functions were annotated according to the metabolic pathway database(KEGG),and the ReporterScore method was used to screen out the differential pathways.Random forest and ROC curve models were used to evaluate the value of gut microbiota in the diagnosis of AIS.Results:1.A total of 216 AIS patients and 198 healthy controls were included for a case-control study.There was no significant difference in age,gender and BMI between the two groups.Species analysis showed that at the species level,Escherichia coli and Shigella were more abundant in AIS patients than healthy people,while the butyrate-producing bacteria Roseburia intestinalis were relatively less in patients with AIS(P adjust<0.05).Functional analysis showed that compared with healthy controls,AIS patients had a higher transport capacity of monosaccharides,but decreased amino acid biosynthesis and vitamin metabolism(P<0.05).Random forest and ROC model show that the predictive value of gut microbiota for the incidence of AIS was 0.921(95%CI:0.874-0.967,P<0.001).2.According to whether the NIHSS score was higher than 4 at the time of admission,they were divided into a mild disease group(n=152)and a severe disease group(n=64).It was found that Bacteroidetes_plebeius and Eubacterium_ractale were enriched in the mild disease group;Lactobacillales and Methanobactericeae were more abundant in the severe disease group(P adjust<0.05).3.During the 90-day follow-up after the onset,6(2.8%)patients were lost to follow-up,and finally 210 patients entered the prognosis analysis,of which 23(11.0%)patients had poor functional outcome.In species analysis,Prevotella were enriched in the good functional outcome group,while Escherichia coli,Proteobacteria and Citrobacter were enriched in the poor functional outcome group(P adjust<0.05).In functional analysis,compared with the good functional outcome group,the poor functional outcome group had higher lecithin biosynthesis and glutamate metabolism pathways,while fatty acid degradation and bile acid synthesis were reduced(P<0.05).Conclusions:1.The composition and function of the gut microbiota in AIS patients have changed.2.The composition of the gut microbiota changes in AIS patients of different severity.3.There are differences in the composition and function of gut microbiota between patients with poor functional outcome and those with good functional outcome.