Dysbiosis of the subgingival microbiome: host-microbial metatranscriptomic analysis during periodontal disease progression and post periodontal treatment

 描述（由申请人提供）：牙周炎是一种由复杂微生物群落的协调作用引起的多种微生物疾病，导致支持牙齿的组织炎症。它是最普遍的致残性健康状况之一，影响全球7.43亿人。在美国，治疗和预防牙周炎的直接支出估计总额接近143亿美元。本研究项目的目标是了解微生物致病的分子机制和宿主对与牙周炎进展相关的微生物挑战的反应。双元转录组学（宿主微生物组）分析提供了了解牙周感染期间致病生物膜和宿主反应中成分的活性和相对重要性所需的信息。为此，我们提出以下具体目标：目标1。通过微生物群-宿主反应表达谱的双转录组分析确定与成人慢性牙周炎进展的初始阶段相关的分子机制。目标2.确定牙周治疗（洁治和根面平整术）对龈下环境稳态的影响。作为DE 021553基金的一部分，我们成功地将后转录组学技术应用于牙周炎进展的研究。由于之前的合作努力（授权DE 021127），我们已经拥有完成本提案所需的所有样本。目标受试者人群将由15名慢性牙周炎个体组成。观察到的微生物变化将与大部分牙周病受试者相关。患者每两个月随访一次，持续12个月的时间，在此期间，他们将接受临床监测以确定哪些样品将用于通过宏基因组学和元转录组学分析比较进展和非进展部位。确定致病所需的关键基因，并提供以下信息 它们的差异表达可用于开发早期诊断、治疗、监测和预防的新靶向方法。此外，潜在的影响超出了牙周炎的研究，因为相同的原理和方法可能适用于其他多种微生物疾病。我们相信，我们为该项目组建的团队具有成功实现本申请中提出的目标的所有资格。

 DESCRIPTION (provided by applicant): Periodontitis is a polymicrobial disease caused by the coordinated action of a complex microbial community, which results in inflammation of tissues that support the teeth. It is one of the most prevalent disabling health conditions, affecting 743 million people worldwide. The total estimated direct expenditures to treat and prevent periodontitis in the US is nearly $14.3 billion. The goal of this research program is to understand the molecular mechanisms of microbial pathogenesis and the host response to the microbial challenge associated with periodontitis progression. Dual metatranscriptomic (hostmicrobiome) analysis provides the information required to understand the activity and relative importance of the constituents in the pathogenic biofilm and host response during periodontal infection. To this end we propose the following Specific Aims: Aim 1. Identify the molecular mechanisms that are associated with the initial stages of adult chronic periodontitis progression by dual-transcriptome analysis of microbiome-host response expression profiles. Aim 2. Determine the effects of periodontal therapy (Scaling and Root Planing) on homeostasis of the subgingival environment. As a part of grant DE021553, we have successfully applied metatranscriptomic techniques to the study of periodontitis progression. Thanks to a previous collaborative effort (grant DE021127) we already have all the samples needed to complete the present proposal. The target subject population will consist of 15 chronic periodontitis individuals. The microbial changes observed will be relevant to a large proportion of subjects with periodontal disease. The patients were followed bimonthly for a period of 12 months, during which they will undergo clinical monitoring to determine which samples will be used for compassion of progressing and non- progressing sites by metagenomic and metatranscriptomic analysis. Identification of critical genes that are required for pathogenesis and information about their differential expression can be used to develop novel targeted approaches to early-stage diagnosis, treatment, monitoring and prevention. Moreover, the potential impact extends beyond the study of periodontitis because the same principles and methods potentially can be applied to other polymicrobial diseases. We believe that the team we have assembled for this project has all the qualifications to accomplish successfully the goals proposed in the present application.