Identification of Uncultivated and Unrecognized Pathogens of Periodontitis

未培养和未被识别的牙周炎病原体的鉴定

基本信息

批准号：
7472583
负责人：
ANNE DENISE HAFFAJEE
金额：
$ 66.76万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2011-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In recent years, studies using molecular techniques have indicated that as many as 700 taxa may be detected in the oral cavity, about 300 or more in subgingival plaque, most of which were uncultivable or at least not recognized. It is likely that some of these uncultivable taxa may be periodontal pathogens. Thus, Specific Aim 1 will test the hypothesis that cultivated or uncultivated bacterial species, not yet recognized as pathogens, are associated with periodontitis. In a cross-sectional study, subgingival biofilm samples, taken from the mesial aspect of up to 28 teeth in each of 80 periodontally healthy and 120 periodontitis subjects. Each sample will be split and individually examined using two microbiological assessments. The first method, direct checkerboard hybridization using whole genomic DNA probes to 40 species, will provide positive and negative controls for known species that discriminate periodontitis from health. Extensive experience indicates that species such as P. gingivalis and T. forsythia will differ significantly from health to disease while most remaining species will not. The second microarray chip assay will detect the presence of 300 taxa; i.e. essentially all of the frequently detected cultivable and as yet uncultivated subgingival taxa. The second major criterion to distinguish periodontal pathogens from non pathogens is based on the notion that suppression of a pathogen should lead to clinical improvement, while failure to reduce that species would lead to disease progression. This criterion will be utilized in Specific Aim 2 which will examine the effects of periodontal therapy on newly recognized potential periodontal pathogens and clinical parameters. The 120 periodontitis subjects from Specific Aim 1 will be treated by SRP and 2 weeks of systemically administered metronidazole and amoxicillin. Clinical monitoring and microbiological sampling will be repeated 3 months post therapy and the subgingival plaque samples examined by the two microbiological methods as described in SA1. Associations will be sought between changes in levels of each test taxon and clinical response to therapy. Since periodontal diseases are infections, it would be difficult to suggest studies that are more important than defining the causative agent(s) of the diseases. This study will examine the association of the uncultivated group of species to periodontal health and disease, thus taking the critical first steps in discriminating the pathogenic from commensal organisms. The identification of such pathogens should, over time, lead to better diagnosis of disease, optimal treatment strategies for the individual patient, new therapeutic approaches and carefully targeted approaches to prevention.

描述（申请人提供）：近年来，利用分子技术的研究表明，口腔中可检测到多达700个类群，龈下菌斑中约300个或更多，其中大多数无法培养或至少无法识别。这些不可培养的类群中的一些可能是牙周病原体。因此，具体目标 1 将检验以下假设：尚未被识别为病原体的培养或未培养的细菌物种与牙周炎相关。在一项横断面研究中，龈下生物膜样本取自 80 名牙周健康受试者和 120 名牙周炎受试者每人多达 28 颗牙齿的近中面。每个样品将被分开并使用两项微生物评估进行单独检查。第一种方法是使用全基因组 DNA 探针对 40 个物种进行直接棋盘杂交，将为已知物种提供阳性和阴性对照，以区分牙周炎和健康。大量经验表明，牙龈卟啉单胞菌和连翘连翘等物种在健康和疾病方面存在显着差异，而大多数其余物种则不会。第二次微阵列芯片检测将检测 300 个类群的存在；即基本上所有经常检测到的可培养和尚未培养的龈下类群。区分牙周病原体和非病原体的第二个主要标准是基于以下概念：抑制病原体应导致临床改善，而未能减少该物种将导致疾病进展。该标准将在具体目标 2 中使用，该目标将检查牙周治疗对新认识的潜在牙周病原体和临床参数的影响。来自具体目标 1 的 120 名牙周炎受试者将接受 SRP 治疗并全身施用甲硝唑和阿莫西林 2 周。治疗后 3 个月将重复进行临床监测和微生物采样，并通过 SA1 中所述的两种微生物方法检查龈下菌斑样本。将寻找每个测试分类单元水平的变化与治疗的临床反应之间的关联。由于牙周病是感染，因此很难提出比确定疾病病原体更重要的研究。这项研究将检查未培养的物种与牙周健康和疾病的关系，从而在区分致病菌和共生生物方面迈出了关键的第一步。随着时间的推移，对这些病原体的识别将有助于更好地诊断疾病、为个体患者提供最佳的治疗策略、新的治疗方法和精心针对性的预防方法。