Gut metagenomics-derived genes as potential biomarkers of Parkinson's disease.
Gut metagenomics-derived genes as potential biomarkers of Parkinson's disease.
复制标题
肠道宏基因组衍生的基因作为帕金森病的潜在生物标志物
DOI：
10.1093/brain/awaa201
复制
发表时间：
2020-08-01
期刊：
影响因子：
--
通讯作者：
Xiao, Qin
中科院分区：
文献类型：
--
作者：
Qian, Yiwei;Yang, Xiaodong;Xiao, Qin
与疾病相关的肠道微生物组组成的鉴定已成为世界范围内的研究热点。新出现的证据表明，帕金森病中存在肠道微生物群失调。在这项研究中，我们的目的是确定与帕金森病相关的肠道微生物组，随后筛选和验证帕金森病的潜在诊断生物标志物。本病例对照研究采用鸟枪法宏基因组测序技术对40名帕金森病患者及其健康配偶粪便中的肠道微生物基因进行了研究。此外，在78名帕金森病患者、75名对照受试者、40名多系统萎缩患者和25名阿尔茨海默病患者的独立中国队列中，用实时PCR验证了所鉴定的特异性肠道微生物基因标记。我们开发了第一个与帕金森病相关的肠道微生物基因目录。25个基因标记物被鉴定为将帕金森病患者与健康对照受试者区分开，实现了0.896的受试者工作特征曲线下面积（AUC）（95%置信区间：83.1-96.1%）。创建了一个高度准确的帕金森病指数，该指数不受疾病严重程度或帕金森病药物的影响。使用定量PCR检测这些基因标记不仅在40对夫妇中区分了帕金森病患者和健康对照组，（AUC = 0.922，95%置信区间：86.4-98.0%），而且在由78名帕金森病患者和75名健康对照受试者组成的独立组中也是如此（AUC = 0.905，95%置信区间：86.0-95.1%）。该分类器还基于25种生物标志物的小组在区分这78名帕金森病患者与40名多系统萎缩患者和25名阿尔茨海默病患者的队列中进行了鉴别诊断能力。根据我们的研究结果，基于肠道微生物组基因集确定的帕金森病指数可能是帕金森病的潜在诊断生物标志物。
Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson's disease. In this study, we aimed to identify the gut microbiome associated with Parkinson's disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson's disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson's disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson's disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease. We developed the first gut microbial gene catalogue associated with Parkinson's disease. Twenty-five gene markers were identified that distinguished Parkinson's disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1-96.1%). A highly accurate Parkinson's disease index, which was not influenced by disease severity or Parkinson's disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson's disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4-98.0%), but also in an independent group of 78 patients with Parkinson's disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0-95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson's disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson's disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson's disease.