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: 9243234
• 负责人: Jorge Frias-Lopez
• 金额: $ 54.98万
• 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/9243234
• 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; Structure; Study Section; 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; public health relevance; scaling and root planing; transcriptome; translational impact; 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（由申请人提供）：牙周炎是一种由复杂微生物群落协调作用引起的多种微生物疾病，会导致支撑牙齿的组织发炎，是最常见的致残性健康状况之一，影响着全世界 7.43 亿人。美国用于治疗和预防牙周炎的直接支出估计总额接近 143 亿美元。该研究计划的目标是了解微生物发病机制和宿主反应的分子机制。双重宏转录组（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。目标 1. 通过微生物组-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始阶段相关的分子机制。 目标 2. 确定。牙周治疗（洁治和牙根规划）对龈下环境稳态的影响作为资助 DE021553 的一部分，我们已成功地将宏转录组学技术应用于牙周炎进展的研究（资助 DE021127）。我们已经拥有完成本提案所需的所有样本。目标受试者群体将包括 15 名慢性牙周炎个体。观察到的微生物变化将与大量患者相关。患有牙周病的受试者每两个月进行一次为期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通过宏基因组和宏转录组分析来识别进展和非进展部位。发病机制所需的关键基因和信息 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，其潜在影响超出了牙周炎的研究范围，因为相同的原理和方法可能适用于其他多种微生物疾病。相信我们为此项目组建的团队拥有成功完成本申请中提出的目标的所有资格。