Objective:To explore the effect of intestinal flora metabolites on neurological rehabilitation after stroke and its mechanism.Methods:From May 2021 to June 2022,132 patients with acute ischemic stroke were recruited continuously.16S ribosomal RNA(rRNA)gene(V3-V4 region)was used to analyze their intestinal microbiota within 24 hours after admission.According to the 3-month mRS score,participants were divided into two groups:better functional group(n=105,mRS 0-2)and poor functional group(n=27,mRS 3-6).0.2 g was separated from each fecal sample,and the contents of total short-chain fatty acids(SCFAs),acetate,propionate,and butyrate were analyzed by gas chromatography/mass spectrometry.Results:Compared with the group with better prognosis,the patients with poor prognosis were older,with higher incidence of hypertension and atrial fibrillation,higher baseline National Institutes of Health Stroke Scale(NIHSS)score and lower the Alberta Stroke Programme Early CT Score applied to diffusion weighted imaging(DWI-ASPECTS)score(P<0.05).The observed species and Chao1 in the poor prognosis group were lower than those in the better prognosis group(P<0.05).Compared with the group with better prognosis,the abundance of six genera(Bacteroides,Enterobacter faecalis,Roche,Ruminococcus,Enterococcus faecalis,and Butyrococcus)producing SCFAs was lower,and all of them reduced significantly in the group with poor prognosis(P<0.05).The median concentrations of total SCFAs,acetate,propionate,and butyrate in patients with poor prognosis were 95.89,64.66,16.72,and 10.14μmol/g,respectively,while those in patients with good prognosis were 119.30,82.05,20.89,and 14.16μmol/g,respectively,and the difference between the two groups was statistically significant,the U values were 3 501,3 509,3 877,and 4 407,respectively(P<0.000 1).Multivariate analysis showed that total SCFAs(OR=12.44,95%CI 1.50-103.07)and butyrate(OR=59.72,95%CI 2.67-1 332.15)were independent risk factors for 90-day dysfunction in stroke patients(P<0.05).Conclusion:The decrease of total SCFAs level,especially butyrate level,is related to the increased risk of 90-day adverse functional outcome in patients with acute ischemic stroke,indicating that SCFAs may be a useful biomarker to identify adverse prognosis.