Association Study Between Stroke Risk And Gut Microbiota On The Basis Of Community Cohort And Its Subgroup Analysis

BackgroundGut microbiota is a newly identified risk factor for stroke,as their intestinal microbiota was significantly disordered.The dysbiosis of gut microbiota could be transferred by Fecal microbiota transplantation,and worsen the brain injury in experimental stroke mice with middle cerebral artery infarction.However,we have no idea about the gut microbial composition before stroke and whether it presents similar dysbiosis characteristics to stroke patients.Mild cognitive impairment is a pathological condition between normal aging and mild dementia.Gut microbiota may play an important role in the development of cognitive dysfunction.However,there is little known about their relationship in China.PurposeBased on the community healthy population with no history of stroke,we used a risk stratification method to explore the gut microbial characteristics of different stroke risk groups.The significance of this study is to explore the condition of gut microbiota before stroke,which laying solid foundation and enlightenment for the subsequent studies on intestinal microbiota of stroke.In addition,a subgroup analysis of mild cognitive impairment was performed and cognitive function assessment was carried.This analysis was aim to determine the impact of gut microbiota on cognitive impairment,which providing clues for microbiota-targeted interventions in the future.MethodsA total of 141 participants aged≥50 years without prior history of stroke were recruited and divided into low-risk,medium-risk and high-risk groups based on known risk factors and whether they were suffering from chronic diseases.At the same time,93 subjects who were willing to finish the cognitive function assessment were included as the subgroup of cognitive function screening.Cognitive function was assessed by the Montreal cognitive assessment basic scale.All participants were required to perform carotid ultrasound examination and their fasting plasma was collected for the detection of intestinal barrier and inflammatory factors.The composition of their gut microbiomes was compared using 16S rRNA gene amplicon next-generation-sequencing and Quantitative Insights into Microbial Ecology(QIIME)analysis.Levels of fecal short-chain fatty acids were measured using gas chromatography.ResultsWe found no significant difference among the three groups in terms of age or gender(Kruskal-Wallis test,Pearson chi-square test,p>0.05).However,white blood cell,neutrophils,and red blood cell counts and high sensitivity C-reactive protein were significantly higher in the HR group than in the LR group.High-density lipoprotein cholesterol was lowest in the HR group.In the pairwise comparison of Bray-Curtis distance,the LR and HR group were obviously disparate(Adonis test,p=0.005),but differences between the LR and MR groups were less significant(Adonis test,p=0.085).Additionally,opportunistic pathogens(e.g.,Enterobacteriaceae and Veillonellaceae)and lactate-producing bacteria(e.g.,Bifidobacterium and Lactobacillus)were enriched,while butyrate-producing bacteria(e.g.,Lachnospiraceae and Ruminococcaceae)were depleted,in the high-risk group compared to the low-risk group.Butyrate concentrations were also lower in the fecal samples obtained from the high-risk group than from the low-risk group.The concentrations of other short-chain fatty acids(e.g.5 acetate,propionate,isobutyrate,isovalerate,and valerate)in the gut were comparable among the three groups.Subgroup analysis revealed that,when compared with the control group,we found the mild cognitive impairment group to be significant sources of variability in terms of gut microbiota(Bray Curtis distance,Adonis test,P<0.05).which was were characterized by the enrichment of proteobacteria,Synergistetes,and lactobacillus.Age,creatinine,average CCAIMT,Crouse score,and plaque numbers were demonstrated to be associated with cognitive impairment.Further multiple logistic regression analysis found that the number of hyperechoic plaques(OR 11.511,95%CI 1.406-94.226,P=0.023)and the abundance of lactobacillus(OR 4.894,95%CI 1.090-21.966,P=0.038)were the important risk factors for mild cognitive impairment.ConclusionParticipants at high risk of stroke were characterized by the enrichment of opportunistic pathogens,low abundance of butyrate-producing bacteria,and reduced concentrations of fecal butyrate.Higher abundance of lactobacillus in the gut holds potential as novel risk factor of people with mild cognitive impairment.Further studies are needed to investigate the underlying role of microorganism in the development of stroke and cognitive impairment.