基于宏基因组技术研究口腔微生物多样性与牙周炎的关系.doc.docVIP

基于宏基因组技术研究口腔微生物多样性 与牙周炎的关系 摘 要：牙周炎是一种影响牙周组织的炎症性疾病。对来自多个牙周炎宏基因组样品的综合分析是检查宿主口腔内微生物多样性和相互作用的有效方法。早前的两项研究共招募了43名受试者使用宏基因组鸟枪测序法分析人的龈下菌斑样品的微生物群落。本文整合了这两项研究的宏基因组序列数据，包括6个健康对照,14个处于稳定期牙周炎的受试者,16个处于进展期牙周炎的受试者,以及7个未知牙周状态的受试者。我们将系统发育分析、丰度显著性差异分析和网络分析应用于综合数据集,以比较不同疾病状态下微生物群落的特征。研究表明，健康受试者具有最高的多样性，而牙周状态处于稳定期的受试者具有最低的多样性。基于此，本文开发了一个基于多样性逻辑模型的朴素分类器,能够很好地预测7个未知牙周状态患者的疾病状态。研究发现口腔微生物群落多样性的丧失与牙周炎的进展之间存在密切关联，这表明宏基因组测序和系统发育分析可预测早期牙周炎，从而有可能进行治疗干预。除牙龈卟啉单胞菌之外，还发现了另外三种与已知的牙周炎病原菌有相似致病特性的病原体,有可能导致牙周炎疾病的发生。 关键词：口腔微生物；牙周炎；宏基因组；多样性； Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis Abstract: Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing. We integrated metagenomic sequence data from those two studies, including six healthy controls, 14 sites representative of stable periodontitis, 16 sites representative of progressing periodontitis, and seven periodontal sites of unknown status. We applied phylogenetic diversity, differential abundance, and network analyses to the integrated dataset to compare microbiological community profiles among the different disease states. We found that healthy subjects had the highest alpha-diversity, while subjects with stable sites had the lowest alpha-diversity. From these results, we developed an alpha-diversity logistic model-based naive classifier able to perfectly predict the disease status of the seven subjects with unknown periodontal status (not used in training). Phylogenetic profiling resulted in the discovery of nine marker microbes, and these species are able to differentiate betwe