肠道菌群介导海马体积萎缩引起AD谱系认知功能下降的探索性研究  

Altered gut microbiota causes cognitive decline of the AD spectrum via mediating the hippocampus atrophy:a pilot study

作　　者：李红艳 闫少珍 卢洁[2] 盛灿 李瑜霞 LI Hong-yan;YAN Shao-zhen;LU Jie;SHENG Can;LI Yu-xia(Department of Neurology,Civil Aviation General Hospital,Beijing 100123,China;Department of Neurology,Xuanwu Hospital of Capital Medical University,Beijing 100053,China;Department of Neurology,Tangshan Central Hospital,Tangshan Hebei 063000,China)

机构地区：[1]民航总医院神经内科,北京100123 [2]首都医科大学宣武医院神经内科,北京100053 [3]唐山中心医院神经内科,河北唐山063000

出　　处：《中国临床医学影像杂志》2023年第10期685-690,共6页Journal of China Clinic Medical Imaging

基　　金：国家自然科学基金(82020108013,82001773)。

摘　　要：目的:探索阿尔茨海默病(AD)连续疾病谱系的肠道微生物变化特征,以及肠道菌群与结构磁共振成像(sMRI)指标的相关性。方法:本研究纳入34名淀粉样蛋白(Aβ)阴性的认知功能正常对照(NC-)和32名Aβ阳性的NC(NC+)受试者以及12名认知障碍(CI)患者,每位受试者均完成临床评估、神经心理学测评、粪便标本采集和sMRI扫描。首先,进行粪便标本16S rRNA扩增子分析,比较三组间肠道菌群的差异。其次,对每位受试者的sMRI数据进行预处理,提取所有受试者特定脑区的灰质指标,包括海马体积和内嗅皮层厚度。采用Spearman相关性分析,探索组间差异肠道菌群与认知量表以及sMRI标记物之间的相关性。最后,采用中介效应分析,评估肠道菌群、影像指标、大脑Aβ沉积程度以及认知功能的相互作用关系。结果:厚壁菌门及其所属的菌群表现出从NC-组到NC+组再到CI组的渐进性下降趋势。厚壁菌门、δ-变形菌纲、脱硫弧菌目、脱硫弧菌科的相对丰度与双侧海马体积呈正相关。基于中介效应发现,厚壁菌门对长延迟回忆、STT-A的作用,以及毛螺旋菌科对STTB的作用受到右侧海马体积的调节,存在显著的间接效应。梭菌纲、梭菌目对右侧海马体积的作用受到Aβ全脑平均标准摄取值比值(SUVR)介导,δ-变形菌纲、脱硫弧菌目、脱硫弧菌科可通过Aβ全脑SUVR介导,调节左侧海马体积。结论:肠道菌群通过改变海马体积从而影响认知功能。Objective:To explore variations in gut microbiota within the spectrum of Alzheimer’s disease(AD)and to ascertain the relationship between altered gut microbiota and structural MRI(sMRI)biomarkers.Methods:In the present study,we recruited 34 Aβnegative NC(NC-)participants,32 Aβpositive NC(NC+)participants and 12 patients with cognitive impairment(CI).Each participant underwent the general clinical estimation,neuropsychological assessments,fecal sample collection,and sMRI scan.First,all participants underwent fecal microbiota analysis through 16S rRNA sequencing technique to compare the difference of microbiota among the three groups.Second,all sMRI data were preprocessed,and gray matter metrics,including hippocampus volume and entorhinal cortex thickness were extracted.Using Spearman correlation analysis,we investigated the association of altered gut microbiota with cognitive function and AD-related neurodegenerative biomarkers.Finally,mediation analysis was used to evaluate the association among gut microbiota,MRI indexes,brain Aβdeposition,and cognition.Results:The relative abundance of phylum firmicutes and its corresponding bacteria exhibited a progressive decline tendency from NC-to NC+and CI.Additionally,firmicutes,deltaproteobacteria,desulfovibrionales,and desulfovibrionaceae showed significant positive correlations with the volume of bilateral hippocampus.Our mediation analysis demonstrated that among all subjects,the abundance of firmicutes had a mediation effect on the performance of AVLT-long delayed recall and STT-A.Moreover,the association between lachnospiraceae and STT-B was also regulated by the right hippocampal volume.The effects of clostridia and clostridiales on the right hippocampal volume were mediated by the SUVR value of the whole brain,while deltaproteobacteria,desulfovibrionales,desulfovibrionaceae affected the left hippocampal volume through whole brain SUVR.Conclusion:Our results indicated that altered gut microbiota may be associated with AD-related neurodegeneration.

关 键 词：阿尔茨海默病 胃肠道微生物组 磁共振成像 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R378[医药卫生—临床医学] R445.2