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非常适合宏基因组研究的疾病模型，因为可以在规定的研究期内监测龋齿发展的时间范围，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但仅部分表征的变化存在明确的联系。我们的研究致力于在关联和纵向研究中确定 60-70 对龋齿不一致的双胞胎中包含牙菌斑微生物组的许多物种的相对丰度。使用不一致的双胞胎对龋齿进行研究所提供的研究功效远远大于使用无关个体进行的类似研究。接下来，我们将通过深度宏基因组测序来比较无龋齿和有龋齿活性的微生物组，以识别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宏转录组研究来确定差异丰富的物种、菌株和基因的功能相关性。所有数据集的统计显着性将被确定，这将允许广泛识别与龋齿和牙齿健康相关的物种、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理解，并可能在未来开发出新的治疗策略。 公共健康相关性：我们的项目直接解决导致龋齿发生和发展的微生物的识别问题。生成的数据将使我们能够识别许多牙齿健康和疾病的诊断标记。这项工作还可能定义龋齿的新疗法。

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.