卒中后认知功能障碍患者肠道菌群紊乱特征研究

Dysbiosis of Gut Microbiota in Patients with Post-Stroke Cognitive Impairment

目的比较卒中后认知功能障碍(post-stroke cognitive impairment,PSCI)患者与健康人群的肠道菌群结构差异,并探讨差异菌种与认知功能的相关性。方法选取24例患者作为PSCI组,同期匹配23例无心脑血管疾病史的健康人群作为对照组。两组均采集粪便标本,采用简易精神状态检查(Mini-Mental State Examination,MMSE)和蒙特利尔认知评估表(Montreal Cognitive Assessment,MoCA)行认知功能评估。采用16S rRNA基因测序技术进行肠道菌群丰度、多样性和差异性分析,通过RDA/CCA分析差异菌种与认知评分的相关性。结果两组一般资料比较及肠道菌群Alpha多样性差异无统计学意义(P>0.05)。组间物种分布比较显示菌群在门和种水平构成存在差异,主要为厚壁菌门、拟杆菌门相对丰度减少和变形菌门相对富集。PSCI组中厚壁菌门的Intestinibacter bartlettii、uncultured bacterium Tyzzerella_3、Fusicatenibacter saccharivorans的相对丰度低于对照组(LDA score>2),且这些细菌与认知功能评分呈正相关,细菌彼此间存在相关性;厚壁菌门的Ruminococcus gnavus、Faecalimonas umbilicata,拟杆菌门的uncultured bacterium Prevotellaceae_NK3B31 group的相对丰度高于对照组(LDA score>2),且这些细菌与认知功能评分呈负相关,细菌彼此间亦存在相关性。结论 PSCI患者与健康对照比较肠道菌群结构特征存在差异,并且与认知功能存在一定相关性,为PSCI的防治提供了新思路。

Objective To identify the differences in the composition of gut microbiota of patients with poststroke cognitive impairment(PSCI) in comparison with the normal cognition healthy controls(HC),and to study the potential association between gut microbiota and cognition function.Methods A total of 24 patients were recruited for the PSCI group,which was matched with 23 healthy subjects with no history of cardiovascular disease recruited over the same period for the control group.Fecal samples were collected for both groups,and Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment(MoCA) were used to evaluate cognitive functions.The abundance,diversity and group difference of gut bacterial communities were determined with 16 S rRNA gene sequencing,and the correlations between differences in bacterial species of the gut microbiota and cognitive function scores were examined with redundancy analysis(RDA)/canonical correspondence analysis(CCA).Results There was no significant difference in the general data or the alpha diversity of gut microbiota between the two groups(P>0.05).Inter-group comparison of microbial species composition revealed differences at the phylum and species levels,mainly represented as reduction in the relative abundance of Firmicutes and Bacteroidetes,and the relative enrichment of Proteobacteria.The relative abundance of Intestinibacter bartlettii,uncultured bacterium Tyzzerella_3,Lactobacillus gasseri,and Fusicatenibacter saccharivorans of phylum Firmicutes in the PSCI patients were significantly reduced in comparison to that of the HC(LDA score>2),and these bacteria were positively correlated with MMSE and MoCA scores.In addition,the Ruminococcus gnavus and Faecalimonas umbilicata of phylum Firmicutes and uncultured bacterium Prevotellaceae_NK3B31 group of phylum Bacteroidetes were significantly enriched in comparison with those of the HC(LDA score>2),and these bacteria were negatively correlated with MMSE and MoCA scores.There were also correlations among these bacteria.Conclusion In this study,we observed compositional differences between the gut microbiota of PSCI patients and those of HC,and revealed that the differences were correlated,to some degree,to the cognitive functions,which will provide new perspectives for the clinical diagnosis and treatment of PSCI.