Metagenomics of the Microbiome in Oral Health and Disease

描述(由申请人提供)：儿童龋齿的发展提供了一种疾病模型，非常适合进行元基因组研究，因为可以在一个确定的研究期间内监测龋齿发展的时间框架，在此期间可以进行纵向研究。龋齿与牙菌斑微生物组的离散变化有很好的联系，但只有部分特征。我们的研究致力于在相关和纵向研究中确定60-70对双胞胎中组成牙菌斑微生物组的许多物种的相对丰度，这些双胞胎与龋齿不一致。使用不协调的双胞胎来治疗龋齿所提供的研究力量比使用无关个体的类似研究要大得多。下一步，我们将通过深度元基因组测序来比较无龋组和有龋组的微生物组，以确定差异丰富的基因和代谢途径。最后，我们将通过进行有针对性的元转录研究来确定不同丰富的物种、菌株和基因的功能相关性。将确定所有数据集的统计意义，以便广泛识别与龋齿和牙齿健康有关的物种、菌株、基因和转录本。这些方法可能会增强我们对龋齿发生和发展的了解，并可能在未来开发新的治疗策略。 公共卫生相关性：我们的项目直接致力于鉴定导致龋齿发生和发展的微生物。生成的数据将使我们能够识别许多牙科健康和疾病的诊断标记物。这项工作也可能定义新的治疗龋齿的方法。

DESCRIPTION (provided by applicant): The development of dental caries in children provides a disease model that is well suited to a metagenomic investigation since the timeframe of caries development can be monitored within a defined study period during which longitudinal studies can be conducted. Dental caries has a well established link to discrete, but only partially characterized changes in the dental plaque microbiome. Our study endeavors to define the relative abundance of many species comprising the dental plaque microbiome in 60- 70 twin pairs discordant for dental caries in association and longitudinal studies. The study power afforded by the use of discordant twin pairs for dental caries is substantially greater than similar studies using unrelated individuals. Next, we will compare the caries-free and caries-active microbiomes by deep metagenomic sequencing to identify differentially abundant genes and metabolic pathways. Lastly, we will determine the functional relevance of differentially abundant species, strains and genes by conducting targeted meta-transcriptomic studies. The statistical significance of all of the datasets will be determined which will allow for the widespread identification of species, strains, genes and transcripts associated with dental caries and dental health. These approaches are likely to enhance our understanding of dental caries onset and development and may enable in the future the development of novel treatment strategies. PUBLIC HEALTH RELEVANCE: Our project directly addresses the identification of microbes that are responsible for the onset and development of dental caries. The data generated will allow us to identify numerous diagnostic markers for dental health and disease. This work may also define novel therapies for dental caries.