New Pathogens for Childhood Caries

描述：儿童早期严重的龋齿会对原牙和恒牙的存活产生负面影响。此外，这种疾病会显著损害儿童的发育。用于评估导致儿童早期严重龋齿（S-ECC）的微生物群的方法存在局限性。特别是那些逃避常规培养或无法培养的细菌，一直被忽视。该应用程序的长期目标是更好地了解龋齿的发病机制。本应用程序的目的是鉴定早期儿童龋齿的微生物病原体。核心假设是，严重和反复发作的早期儿童龋齿是由一种特定的细菌亚群引起的，这些细菌是强酸性物质的产生者。该应用程序的基本原理是，它将提供一套全面的物种，可以评估它们与复发性疾病的关系，并在未来的研究中，用于预测龋齿的能力，并作为发展预防和治疗这种感染的目标物种。患病儿童和健康儿童的微生物群将被识别和比较。中心假设将通过两个特定目标进行验证：1)确定严重早期儿童龋齿的候选细菌病原体。工作假设是，与没有龋齿的儿童相比，S-ECC的微生物群丰富了与疾病相关的物种。2)确定复发性早期儿童龋齿的候选细菌病原体。工作假设是重度龋齿患儿的复发性龋齿菌群比无龋齿患儿丰富，且S-ECC患儿治疗后无龋齿复发。该创新方法将从DNA扩增的细菌16S rRNA基因的克隆和测序与培养方法相结合，以丰富和测试分离物的产酸能力。在拟议的研究结束时，预计将确定新的致龋病原体，并建立一个微生物谱，以预测严重疾病的可能性。这项研究具有重要意义，因为它有望提供工具，大大提高我们预测严重和复发性早期儿童龋齿发展的能力，并指出哪些物种需要抑制才能有效治疗。因此，预计这一疾病的许多不良后果将得以避免，随之而来的牙科和相关医疗费用也将减少。

DESCRIPTION: Severe early childhood caries negatively affects the survival of the primary and permanent dentitions. Furthermore, the disease can markedly impair child development. There are limitations in methods that have been used to evaluate the microbiota that is responsible for severe early childhood caries (S-ECC). In particular, bacteria that evade routine culture, or have been uncultivable, have been overlooked. The long-term goal of the application is to better understand the pathogenesis of dental caries. The objective of this application is to identify the microbial pathogens of early childhood caries. The central hypothesis is that severe and recurrent early childhood caries is caused by a specific sub-set of bacterial species that are strong acid producers. The rationale for the application is that it will provide a comprehensive set of species that can be evaluated for their association with recurrent disease, and, in future studies, for their ability to predict caries, and as target species in the development of prophylaxis and treatment for this infection. The microbiota of diseased and healthy children will be identified and compared. The central hypothesis will be tested with two Specific Aims: 1) Identify candidate bacterial pathogens for severe early childhood caries. The working hypothesis is that the microbiota of S-ECC is enriched for disease-associated species compared to caries-free children. 2) Identify candidate bacterial pathogens for recurrent early childhood caries. The working hypothesis is that the microbiota of recurrent caries in children treated for severe caries is enriched for cariogenic pathogens compared with the microbiota of caries-free children, and S-ECC children not showing caries recurrence post-therapy. The innovative approach will combine cloning and sequencing bacterial 16S rRNA genes amplified from DNA with cultural methods to enrich for, and test acid producing ability of isolates. At the conclusion of the proposed research, it is expected that new cariogenic pathogens will be identified, and a microbiological profile that will be predictive of the potential for severe disease. The proposed research is significant because it is expected to provide tools to substantially improve our ability to predict the development of severe and recurrent early childhood caries, and indicate which species need suppression for effective therapy. As a result, it is expected that many of the negative consequences of this disease will be avoided, with attendant reductions in the costs of dental and related medical care.