载脂蛋白 E4 基因与阿尔茨海默病肠道微生物群的相关性。

Correlation between APOE4 gene and gut microbiota in Alzheimer's disease.

机构信息

Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China P.R.

Clinical Skills Training Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China P.R.

出版信息

Benef Microbes. 2023 Sep 1;14(4):349-360. doi: 10.1163/18762891-20220116.

DOI:10.1163/18762891-20220116

PMID:38661357

Abstract

Gut microbiota (GM) dysbiosis has been increasingly associated with Alzheimer's disease (AD). However, the association between APOE4, the most common genetic risk factor for sporadic AD, and GM in AD remains unclear. In this study, we conducted a comparative analysis of the GM of participants from China and the USA, with and without APOE4 genes and with or without AD (67 AD cases, 67 control cases). Our results revealed that the GM alpha diversity was not different between groups (AD_APOE4, Control_APOE4, AD_non-APOE4, and Control_non-APOE4) (419.031 ± 143.631 vs 391.091 ± 126.081, 351.086 ± 169.174 and 386.089 ± 177.200, respectively. P > 0.05). Interestingly, individuals in the AD_APOE4 group had different bacterial compositions and bacterial biomarkers. The Kruskal-Wallis rank sum test indicated that the abundances of many bacterial species in the AD_APOE4 patients differed from those in control individuals, including decreases in unclassified_g__Escherichia-Shigella (1.763 ± 6.73, 4.429 ± 11.13, 8.245 ± 16.55, and 5.69 ± 13.91 in four groups, respectively; P < 0.05), and unclassified_g_Clostridium_sensu_stricto_1 (0.1519 ± 0.348, 2.502 ± 5.913, 0.5146 ± 0.9487, 1.063 ± 3.428 in four groups, respectively; P < 0.05), and increases in gut_metagenome_g_Faecalibacterium (2.885 ± 4.47, 2.174 ± 3.957, 0.5765 ± 1.784, 1.582 ± 2.92 in four groups, respectively. P < 0.01) and unclassified_g_Bacteroides (3.875 ± 3.738, 2.47 ± 2.748, 2.046 ± 3.674, 3.206 ± 3.446 in four groups, respectively; P < 0.05). In the KEGG pathway level 2 analysis, we identified three significant differences in relative abundances of predicted functions between AD_APOE4 and AD_non-APOE4_carrier groups: neurodegenerative diseases (0.0007 ± 0.0005 vs 0.0009 ± 0.0004; P < 0.01), metabolism (0.0240 ± 0.0003 vs 0.0250 ± 0.0003; P < 0.05), and biosynthesis of other secondary metabolites (0.0094 ± 0.0002 vs 0.0090 ± 0.0002; P < 0.05). Receiver operating characteristic curves further demonstrated an area under the curve (AUC) of 0.74 for the discrimination of AD_APOE4_carrier and AD_non-APOE4_carrier individuals.

摘要

肠道微生物群（GM）失调与阿尔茨海默病（AD）的关联性日益增加。然而，APOE4 基因（AD 最常见的遗传风险因素）与 AD 中的 GM 之间的关联仍不清楚。在这项研究中，我们对来自中国和美国的参与者的 GM 进行了比较分析，这些参与者携带或不携带 APOE4 基因，以及是否患有 AD（67 例 AD 病例，67 例对照病例）。我们的结果表明，各组的 GM 多样性alpha 无差异（AD_APOE4、Control_APOE4、AD_non-APOE4 和 Control_non-APOE4）（419.031±143.631 与 391.091±126.081、351.086±169.174 和 386.089±177.200，分别，P>0.05）。有趣的是，AD_APOE4 组的个体具有不同的细菌组成和细菌生物标志物。Kruskal-Wallis 秩和检验表明，AD_APOE4 患者的许多细菌种类的丰度与对照个体不同，包括未分类_g__Escherichia-Shigella（1.763±6.73、4.429±11.13、8.245±16.55 和 5.69±13.91，分别在四个组中；P<0.05）和未分类_g_Clostridium_sensu_stricto_1（0.1519±0.348、2.502±5.913、0.5146±0.9487 和 1.063±3.428，分别在四个组中；P<0.05）减少，以及 gut_metagenome_g_Faecalibacterium（2.885±4.47、2.174±3.957、0.5765±1.784 和 1.582±2.92，分别在四个组中；P<0.01）和未分类_g_Bacteroides（3.875±3.738、2.47±2.748、2.046±3.674 和 3.206±3.446，分别在四个组中；P<0.05）增加。在 KEGG 途径水平 2 分析中，我们确定了 AD_APOE4 和 AD_non-APOE4 携带者组之间相对丰度存在三个显著差异的预测功能：神经退行性疾病（0.0007±0.0005 与 0.0009±0.0004；P<0.01）、代谢（0.0240±0.0003 与 0.0250±0.0003；P<0.05）和其他次生代谢物的生物合成（0.0094±0.0002 与 0.0090±0.0002；P<0.05）。接收者操作特征曲线进一步证明 AD_APOE4 携带者和 AD_non-APOE4 携带者个体的区分的曲线下面积（AUC）为 0.74。