Gut microbiome alterations in Alzheimer’s disease. Gut microbiome alterations in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.

阿尔茨海默病（Alzheimer’s disease, AD）是最常见的痴呆类型。然而，这一毁灭性疾病的发病机制尚未完全阐明。近期针对啮齿类动物的研究表明，肠道微生物组的改变可能参与淀粉样蛋白沉积的发生过程，但目前尚未在人类群体中明确与AD相关的微生物群落特征。为此，我们对确诊为AD相关性痴呆的参与者及非痴呆参与者的粪便样本进行了细菌分类组成特征分析。分析结果显示，AD患者的肠道微生物组多样性显著降低，且其群落组成与年龄、性别匹配的健康对照人群存在明显差异。我们鉴定出了从菌门到菌属水平的细菌丰度差异：AD患者肠道微生物组中厚壁菌门（Firmicutes）丰度降低、拟杆菌门（Bacteroidetes）丰度升高，双歧杆菌属（Bifidobacterium）丰度降低。此外，我们观察到差异丰度菌属的水平与AD患者脑脊液（cerebrospinal fluid, CSF）生物标志物之间存在显著相关性。本研究结果将AD纳入了与肠道微生物组改变相关的疾病谱，并提示肠道菌群可能成为治疗干预的潜在靶点。