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

 描述(申请人提供)：牙周炎是一种多菌疾病，由复杂微生物群落的协调作用引起，导致支持牙齿的组织发炎。它是最普遍的致残性健康疾病之一，影响着全球7.43亿人。据估计，美国用于治疗和预防牙周炎的直接支出总额接近143亿美元。这项研究的目标是了解微生物致病的分子机制，以及宿主对与牙周炎进展相关的微生物挑战的反应。双重转译(宿主微生物组)分析提供了所需的信息，以了解致病生物膜中成分的活性和相对重要性，以及在牙周感染期间宿主的反应。为此，我们提出了以下具体目标：目的1.通过对微生物组-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初期相关的分子机制。目的2.确定牙周治疗(洁治和根面平整)对龈下环境动态平衡的影响。作为DE021553基金的一部分，我们已经成功地将后翻译技术应用于牙周炎进展的研究。由于之前的合作努力(赠款DE021127)，我们已经拥有完成本提案所需的所有样本。目标受试者将包括15名慢性牙周炎患者。观察到的微生物变化将与很大比例的牙周病患者相关。每两个月对患者进行一次为期12个月的随访，在此期间，他们将接受临床监测，以确定哪些样本将用于对进展和非进展部位的同情，通过元基因组和元翻译分析。识别致病所需的关键基因和有关 它们的差异表达可用于开发新的有针对性的早期诊断、治疗、监测和预防方法。此外，潜在的影响超出了牙周炎的研究范围，因为同样的原理和方法可能也适用于其他多菌疾病。我们相信，我们为这个项目组建的团队有资格成功实现本申请中提出的目标。

 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.