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李亚梅, 余茜, 黄林, 等. 卒中后早期认知下降患者肠道菌群改变与认知功能的相关性[J]. 四川大学学报(医学版), 2022, 53(5): 857-865. DOI: 10.12182/20220960105
引用本文: 李亚梅, 余茜, 黄林, 等. 卒中后早期认知下降患者肠道菌群改变与认知功能的相关性[J]. 四川大学学报(医学版), 2022, 53(5): 857-865. DOI: 10.12182/20220960105
LI Ya-mei, YU Qian, HUANG Lin, et al. Correlations Between Gut Microbiota Changes and Cognitive Function in Patients with Post-Stroke Cognitive Impairment in the Early Stage[J]. Journal of Sichuan University (Medical Sciences), 2022, 53(5): 857-865. DOI: 10.12182/20220960105
Citation: LI Ya-mei, YU Qian, HUANG Lin, et al. Correlations Between Gut Microbiota Changes and Cognitive Function in Patients with Post-Stroke Cognitive Impairment in the Early Stage[J]. Journal of Sichuan University (Medical Sciences), 2022, 53(5): 857-865. DOI: 10.12182/20220960105

卒中后早期认知下降患者肠道菌群改变与认知功能的相关性

Correlations Between Gut Microbiota Changes and Cognitive Function in Patients with Post-Stroke Cognitive Impairment in the Early Stage

  • 摘要:
      目的  观察卒中后1个月内认知下降患者肠道菌群构成改变,并探讨差异菌类与认知功能等临床指标的相关性。
      方法  采用横断面研究设计,分别选取卒中伴认知障碍 (PSCI组)、卒中不伴认知障碍(Non-PSCI组)和对照者(NC组)各12例。收集各组人群一般资料及临床指标。采用16S rRNA基因测序技术进行肠道菌群丰度、多样性及差异性分析,分析肠道菌群与临床指标的相关性及差异菌类对认知下降的鉴别效能。
      结果  PSCI组简易精神状态检查(Mini-Mental State Examination, MMSE)和蒙特利尔认知评估(Montreal Cognitive Assessment, MoCA)得分低于Non-PSCI组(P<0.001),3组间其他一般资料和临床指标及肠道菌群Alpha多样性比较差异无统计学意义(P>0.05)。3组间肠道菌群在门、属、种水平构成上存在差异。门水平,PSCI组放线菌门相对丰度明显增加(LDA score>2)。属和种水平,3组排列前10的菌类以厚壁菌门多样性最高,相对丰度Non-PSCI组中疣微菌门呈增加趋势,PSCI组中放线菌门呈增加趋势。组间差异性分析显示各组存在不同的标志菌类,其中PSCI组放线菌门的Bifidobacterium属、Alloscardovia属和Alloscardovia omnicolens菌及厚壁菌门的Lactobacillus gasseri菌和Anaerostipes hadrus菌明显升高(LDA score>2),且相关性分析提示Anaerostipes hadrus菌与MoCA呈负相关,Bifidobacterium属与血尿酸呈正相关。Bifidobacterium属、Lactobacillus gasseri菌和Anaerostipes hadrus菌对区分有无认知下降有一定鉴别效能,曲线下面积分别为0.785、0.792、0.750(P<0.05)。
      结论  卒中后早期认知下降患者肠道菌群结构发生改变,差异菌类与认知功能及相关危险因素存在一定相关性,为卒中后认知障碍的早期防治提供新的切入点。

     

    Abstract:
      Objective  To observe the changes in the composition of gut microbiota in stroke patients showing cognitive impairment within one month after the stroke, and to explore the correlation between bacteria presenting dissimilarity and cognitive functions and other clinical indicators.
      Methods  A cross-sectional study was conducted, involving 12 patients with post-stroke cognitive impairment (PSCI group), 12 stroke patients without cognitive impairment (Non-PSCI group), and 12 healthy volunteers in a normal control group (NC group). The demographic and clinical data were gathered. The abundance, diversity and dissimilarity of gut bacterial communities were determined by 16S rRNA gene sequencing. Then, we studied the correlation between gut microbiota and clinical characteristics and the effectiveness of using microbiome markers to identify cognitive decline.
      Results  The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores of the PSCI group were significantly lower than those the Non-PSCI group (P<0.001). There was no significant intergroup difference in the demographic data, the clinical data, and the Alpha diversity of gut microbiota among the three groups (P>0.05). Microbial composition analysis of the three groups revealed proportion alternations at the phylum, genus and species levels. At the phylum level, linear discriminant analysis (LDA) effect size (LEfSe) analysis suggested that the Actinomycetes had significantly increased relative abundance in the PSCI group (LDA score>2). At the genus and species levels, Firmicutes had the highest diversity among the top 10 bacteria in the three groups, while the relative abundance of Verrucomicrophyla presented an increasing trend in the Non-PSCI group and that of Actinobacteria showed an increasing trend in the PSCI group. Further LEfSe analysis revealed that there were different microbiome markers in each group, among which the Bifidobacterium, Alloscardovia, and Alloscardovia omnicolens of the phylum Actinomycetes and Lactobacillus gasseri and Anaerostipes hadrus of the phylum Firmicutes in the PSCI group increased significantly (LDA score>2). Correlation analysis indicated that Anaerostipes hadrus was negatively correlated with the MoCA scores, while Bifidobacterium was positively correlated with blood uric acid (UA). Bifidobacterium, Lactobacillus gasseri and Anaerostipes hadrus could be used to distinguish PSCI patients from Non-PSCI patients, presenting an area under the curve of 0.785, 0.792 and 0.750, respectively (P<0.05).
      Conclusion  Stroke patients with cognitive impairment in the early stage showed composition changes in their gut microbiota, and the bacteria exhibiting dissimilarity were correlated, to some degree, with cognitive function and related risk factors, which could provide new clues for the early management of PSCI.

     

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