Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P.R. China.
Department of Biostatistics, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P.R. China.
Brain. 2020 Aug 1;143(8):2474-2489. doi: 10.1093/brain/awaa201.
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.
肠道微生物组与疾病的关联已成为全球研究热点。新出现的证据表明，帕金森病患者存在肠道微生物失调。在这项研究中，我们旨在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。这项病例对照研究使用 shotgun 宏基因组测序分析了 40 名中国帕金森病患者及其健康配偶粪便中的肠道微生物基因。此外，我们还在一个独立的中国帕金森病患者队列（78 名帕金森病患者、75 名对照、40 名多系统萎缩患者和 25 名阿尔茨海默病患者）中使用实时 PCR 验证了鉴定出的特定肠道微生物基因标志物。我们开发了与帕金森病相关的第一个肠道微生物基因目录。确定了 25 个基因标志物，可将帕金森病患者与健康对照区分开来，其受试者工作特征曲线下面积（AUC）为 0.896（95%置信区间：83.1-96.1%）。创建了一个不受疾病严重程度或帕金森病药物影响的高度准确的帕金森病指数。使用定量 PCR 测试这些基因标志物不仅可以区分 40 对患者（AUC=0.922，95%置信区间：86.4-98.0%），还可以区分 78 名帕金森病患者和 75 名健康对照者（AUC=0.905，95%置信区间：86.0-95.1%）。该分类器还可以根据 25 个生物标志物面板，将这 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进行区分，从而实现鉴别诊断能力。基于我们的结果，基于肠道微生物组基因集的鉴定出的帕金森病指数可能是帕金森病的潜在诊断生物标志物。
