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个非常适合宏基因组研究的疾病模型，因为可以在确定的研究期间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变化有很好的联系，但只是部分表征。我们的研究试图确定60- 70对在关联研究和纵向研究中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的研究能力比使用不相关个体的类似研究要大得多。接下来，我们将通过深度宏基因组测序来比较无龋和有龋活性的微生物组，以确定差异丰富的基因和代谢途径。最后，我们将通过针对性的meta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。将确定所有数据集的统计意义，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。这些方法可能会提高我们对龋齿发生和发展的理解，并可能在未来开发新的治疗策略。

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.