New Pathogens for Childhood Caries

描述：严重的儿童早期龋齿对乳牙和恒牙的存活率有负面影响。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的微生物区系(S-ECC)的方法存在局限性。特别是，逃避常规培养或无法培养的细菌被忽视了。该应用的长期目标是更好地了解龋齿的发病机制。这项应用的目的是鉴定儿童早期龋病的微生物病原体。中心假设是，严重和反复的儿童早期龋病是由一组特定的细菌亚种引起的，这些细菌产生强酸。应用的理由是，它将提供一套全面的物种，可以评估它们与复发疾病的联系，以及在未来的研究中，评估它们预测龋齿的能力，并作为开发这种感染的预防和治疗的目标物种。疾病儿童和健康儿童的微生物区系将被识别和比较。核心假设将以两个具体目标进行检验：1)确定严重儿童早期龋病的候选细菌病原体。工作假说是，与无龋齿的儿童相比，S-ECC的微生物群中富含与疾病相关的物种。2)确定儿童复发性龋病的候选病原菌。工作假说是，与无龋组相比，接受严重龋病治疗的儿童复发龋菌群中的致龋性病原体丰富，并且S-ECC儿童在治疗后没有出现龋病复发。这一创新的方法将把从DNA中扩增出的细菌16S rRNA基因的克隆和测序与培养方法相结合，以丰富和测试菌株的产酸能力。在拟议的研究结束时，预计将确定新的致龋性病原体，并将确定预测可能发生严重疾病的微生物图谱。这项拟议的研究意义重大，因为它有望提供工具，大幅提高我们预测儿童早期严重和复发龋齿发展的能力，并指明哪些物种需要抑制才能有效治疗。因此，预计这种疾病的许多负面后果将被避免，随之而来的是牙科和相关医疗保健费用的减少。

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.