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

龈下微生物群失调：牙周病进展和牙周治疗后宿主微生物宏转录组分析

• 批准号: 9373978
• 负责人: Jorge Frias-Lopez
• 金额: $ 42.36万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-18 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9373978
• 关键词: Adult; Affect; Anabolism; Cardiovascular Diseases; Chemotaxis; Clinical; Communities; Compassion; Complex; Data; Development; Diabetes Mellitus; Diagnosis; Direct Expenditure; Disease; Disease Progression; Environment; Future; Gene Expression; Genes; Genetic Markers; Goals; Grant; Health; Homeostasis; Immune response; Individual; Inflammation; Inflammatory Response; Insurance; Iron; Knowledge; Lead; Light; Lipid A; Metabolic; Metagenomics; Methods; Microbial Biofilms; Molecular; Molecular Profiling; Monitor; Organism; Outcome; Pathogenesis; Pathogenicity; Patients; Periodontal Diseases; Periodontal Infection; Periodontitis; Population; Prevention; Preventive treatment; Proteins; Research; Role; Sampling; Series; Site; Solid; Staging; Structure; Study Section; Taxon; Techniques; Testing; Time; Tissues; Tooth structure; Virulence Factors; Work; base; cell motility; cytokine; diagnostic biomarker; differential expression; isoprenoid; microbial; microbial community; microbial host; microbiome; novel; oral biofilm; oral microbiome; pathogen; prevent; programs; scaling and root planing; transcriptome; treatment response

 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.

 描述（由适用提供）：牙周炎是由复杂微生物群落的协调作用引起的多种疾病，这导致了支撑牙齿的时机发炎。它是最普遍的禁用健康状况之一，影响了全球7.43亿人。在美国治疗和预防牙周炎的总估计直接支出近143亿美元。该研究计划的目的是了解微生物发病机理的分子机制以及对与牙周炎进展相关的微生物挑战的宿主反应。双元转录组（宿主微生物组）分析提供了了解牙周感染期间病原生物膜和宿主反应的活性和相对重要性所需的信息。为此，我们提出了以下特定目的：目标1。确定与成年慢性牙周炎进展的初始阶段相关的分子机制，通过对微生物组宿主宿主反应表达谱的双转录组分析。目标2。确定牙周疗法（缩放和根计划）对次命环境体内稳态的影响。作为Grant DE021553的一部分，我们成功地将元文字技术应用于牙周炎进展的研究。感谢以前的合作努力（Grant DE021127），我们已经拥有完成本建议所需的所有样本。目标受试者将由15个慢性牙周炎个体组成。观察到的微生物变化将与大量患有牙周疾病的受试者有关。两名患者在12个月的时间内进行了临床监测，以确定哪些样品将通过元基因组和元文字分析来用于进步和非进步位点的同情。鉴定发病机理所需的关键基因和有关的信息 它们的差异表达可用于开发新颖的靶向方法，用于早期诊断，治疗，监测和预防。此外，潜在的影响范围超出了牙周炎的研究，因为相同的原理和方法可能可以应用于其他多数型疾病。我们认为，我们为该项目组装的团队具有成功实现本应用程序中提出的目标的所有资格。