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阿尔茨海默病患者肠道菌群改变与认知功能损伤的相关性

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目的 探讨阿尔茨海默病(Alzheimer's disease,AD)患者肠道菌群改变及其与认知功能损伤相关性.方法 根据临床痴呆评定量表(CDR),将35例AD患者分为轻中度组(n=15)和重度组(n=20),收集两组患者的粪便样本,对粪便标本进行16S rRNA高通量测序分析粪便中微生物群的组成和肠道菌群β多样性.采用调查问卷及量表调查AD患者的一般情况、抑郁状态及认知损伤程度.通过血液检测AD患者白细胞、甘油三酯、胆固醇、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)、载脂蛋白E(ApoE)、脂蛋白a(Lpa)、血糖(Glu)、糖化血红蛋白(HbA1c),采用R软件进行粪便菌群与上述指标的相关性分析.结果 AD重度组简易精神状态检查量表(MMSE)、重复性成套神经心理状态测验(RBANS)分值均低于AD轻中度组(P<0.01).肠道菌群β多样性分析结果提示两组间菌群多样性差异有统计学意义(P<0.05).重度组和轻中度组肠道菌门相对丰度及属相对丰度差异都有统计学意义(P<0.05).AD患者大肠杆菌、志贺菌与Lpa呈正相关(P<0.01),与LDL呈负相关(P<0.05);双歧杆菌与RBANS、高脂血症呈正相关(P<0.05),与Lpa呈负相关(P<0.01);克雷伯杆菌与病程、CDR呈正相关(P<0.01);阿克曼菌与HLP呈负相关(P<0.05);肠球菌与CDR呈正相关(P<0.05);乳酸杆菌与年龄呈正相关(P<0.05);粪杆菌与CDR、病程、年龄和MMSE负相关(P<0.05).结论 AD患者伴随肠道菌群的改变,AD患者认知功能的损伤及其严重程度与肠道菌群多样性和相对丰度有关.
Correlation between gut microbiota and cognitive impairment in Alzheimer's disease patients
Objective To explore the changes of gut microbiota in Alzheimer's disease(AD)patients and their correlation with cognitive impairment.Methods According to the Clinical Dementia Rating Scale(CDR),35 AD patients were divided into mild to moderate group(n=15)and severe group(n=20).Fecal samples were collected to analyze the composition of microbiota and β diversity of gut microbiota by high-throughput 16S rRNA sequencing.Survey questionnaires and scales were used to investigate the general situation,the depression status,and the degree of cognitive impairment of AD patients.The levels of white blood cells,triglycerides,cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),apolipoprotein A(ApoA),ApoB,ApoE,lipoprotein a(Lpa),blood glucose(Glu),glycated hemoglobin(HbAlc)in AD patients were detected.The correlations between the fecal microbiota and the above indicators were conducted using R software.Results The scores of the Mini Mental State Examination(MMSE)and the Repe-titive Neuropsychological State Test(RBANS)in severe group were lower than those in mild to moderate group(P<0.01).Intestinal microbiota analysis results indicated that there was a statistical difference in β diversity between the two groups(P<0.05).The relative abundances of gut microbiota phylum and genus showed significant difference between the two groups(P<0.05).Escherichia coli and Shigella were positively correlated with Lpa(P<0.01),but negatively correlated with LDL(P<0.05).Bifidobacterium was positively correlated with RBANS and HLP(P<0.05),but negatively correlated with Lpa(P<0.01).Klebsiella pneumoniae was positively correlated with disease course and CDR(P<0.01),Akkermansia was negatively correlated with hyperlipidemia,Enterococcus was positively correlated with CDR(P<0.05),and Lactobacillus was positively correlated with age(P<0.05).Fecal bacteria were negatively correlated with CDR,disease duration,age,and MMSE(P<0.05).Conclusion The changes of gut microbiota are associated with AD patients,and the cognitive impairment and the severity of AD patients are related to the diversity and the relative abundance of gut microbiota.

Alzheimer's diseaseseverityintestinal microbiotacognitive function16S ribosomal RNA sequencing technologycommunity diversity

杨庚林、白布加甫·高娃、居西昆·阿合买提、哈米萨木·艾合买提江

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乌鲁木齐市第四人民医院临床心理科,乌鲁木齐 830000

乌鲁木齐市友爱医院临床心理科

乌鲁木齐市妇幼保健院临床心理科

阿尔茨海默病 严重程度 肠道菌群 认知功能 16S核糖体RNA测序技术 菌群多样性

乌鲁木齐市卫生健康委科技计划项目

202028

2024

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子:0.931
ISSN:1007-6611
年,卷(期):2024.55(8)