阿尔茨海默病肠道菌群相对丰度与认知功能的关系

Correlation between Relative Abundance of Gut Microbiome and Cognitive Function in Alzheimer′s Disease

目的探讨阿尔茨海默病(AD)肠道菌群相对丰度与认知功能的关系。方法选取2018年5月至2019年5月北京中医药大学东直门医院脑病三科门诊、病房及社区招募的61例受试者作为研究对象,根据诊断标准分为正常对照(NC)组(21例)、遗忘型轻度认知损害(aMCI)组(20例)、AD组(20例)。采用简易精神状态检查表(MMSE)评估受试者总体认知功能,延迟故事回忆(DSR)评估情景记忆,日常生活能力量表评估日常生活能力,临床痴呆评定量表评估认知损害的程度。对粪便样品进行16S核糖体RNA高通量测序,对所有序列进行OTU归类,获得细菌分类和细菌相对丰度。比较3组差异肠道菌群相对丰度并分析其与认知功能的相关性。结果 AD组的MMSE、DSR评分均低于NC组和aMCI组,ADL、CDR评分均高于NC组和aMCI组(P<0.05);aMCI组的DSR评分低于NC组(P<0.01),CDR评分高于NC组(P<0.01)。AD组的β变形菌纲、伯克菌目、产碱杆菌科、萨特菌属相对丰度均高于NC组(P<0.05),厚壁菌门、梭菌纲、梭菌目、梭菌科相对丰度低于NC组(P<0.05);aMCI组的产碱杆菌科、萨特菌属相对丰度高于NC组(P<0.05),厚壁菌门、梭菌纲、梭菌目相对丰度低于NC组(P<0.05)。不同分类水平上厚壁菌门、梭菌纲、梭菌目、梭菌科相对丰度与MMSE评分呈正相关(P<0.05),β变形菌纲、伯克菌目、产碱杆菌科、萨特菌属相对丰度与MMSE评分呈负相关(P<0.05);不同分类水平上厚壁菌门、梭菌纲、梭菌目、梭菌科相对丰度与DSR评分呈正相关(P<0.05),β变形菌纲、伯克菌目、产碱杆菌科、萨特菌属相对丰度与DSR评分呈负相关(P<0.05)。结论拟杆菌门、厚壁菌门、梭菌纲、β变形菌纲及其部分下属菌群与AD认知功能有关,可能对AD发病及进展有影响。

Objective To explore the relationship between relative abundance of gut microbiome and cognitive function in Alzheimer′s disease(AD).Methods A total of 61 subjects recruited from Department Three of Encephalopathy, Ward of Dongzhimen Hospital, Beijing University of Chinese Medicine as well as the community from May 2018 to May 2019 were included.They were divided into a normal control(NC) group(21 cases),an amnestic mild cognitive impairment(aMCI) group(20 cases) and an AD group(20 cases) according to the diagnostic criteria.Mini-mental state examination(MMSE) was used to evaluate the overall cognitive function, delayed story recall(DSR) was used to evaluate episodic memory, activities of daily living scale was used to evaluate abilities of daily living, and clinical dementia rating was used to assess the degree of cognitive impairment.High throughput 16 S ribosomal RNA sequencing was performed on fecal samples, and operational taxonomic units(OTU) classification was performed on all sequences to obtain bacterial classification and bacterial relative abundance.The relative abundance of gut microbiome was compared among the three groups, and its correlation withcognitive function was analyzed.Results The MMSE and DSR scores in the AD group were lower than those in the NC group and aMCI group, and the ADL and CDR scores in the AD group were higher than those in the NC group and aMCI group(P<0.05).The DSR score of the aMCI group was lower than that of the NC group(P<0.01),and the CDR score of the aMCI group was higher than that of the NC group(P<0.01).The relative abundances of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Sutterella in the AD group were all higher than those in the NC group(P<0.05),and the relative abundances of Firmicutes, Clostridia, Clostridiales, Clostridiaceae in the AD group were lower than those in the NC group(P<0.05).The relative abundances of Alcaligenaceae and Sutterella in the aMCI group were higher than those in the NC group(P<0.05),and the relative abundances of Firmicutes, Clostridia and Clostridiales in the aMCI group were lower than those in the NC group(P<0.05).At different taxonomic levels, the relative abundances of Firmicutes, Clostridia, Clostridiales and Clostridaceae were positively correlated with MMSE score(P<0.05),while the relative abundances of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Sutterella were negatively correlated with MMSE score(P<0.05).At different taxonomic levels, Firmicutes, Clostridia, Clostridiales and Clostridiaceae were positively correlated with DSR score(P<0.05) while Betaproteobacteria, Burkholderiales, Alcaligenaceae, and Sutterella were negatively correlated with DSR score(P<0.05).Conclusion Bacteroidetes, Firmicutes, Clostridia, Betaproteobacteria and some of their subordinate bacteria are related to the cognitive function of AD,which may affect the pathogenesis and progression of AD.