Metagenomics of the Microbiome in Oral Health and Disease

口腔健康和疾病中微生物组的宏基因组学

• 批准号: 8309795
• 负责人: Karen E. Nelson
• 金额: $ 68.51万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-16 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309795
• 关键词: Accounting; Acids; Address; Affect; Attention; Behavioral; Biochemical; Biochemical Pathway; Categories; Child; Childhood; Chronic Disease; Code; Communities; Competence; DNA Sequence; Data; Data Set; Dental Care; Dental Plaque; Dental caries; Development; Diagnostic; Dietary Practices; Disease; Disease model; Etiology; Exposure to; Future; Gene Expression Profile; Gene Targeting; Genes; Genetic Transcription; Genomics; Goals; Human; Individual; Infant; Investigation; Knowledge; Link; Longitudinal Studies; Metabolic Pathway; Metabolism; Metagenomics; Methodology; Microbe; Microbial Biofilms; Microbial Genetics; Modeling; Monitor; Mouth Diseases; Natural History; Oral cavity; Oral health; Organism; Participant; Pathway interactions; Pattern; Positioning Attribute; Production; Regulatory Pathway; Relative (related person); Research; Research Project Grants; Role; Streptococcus mutans; Techniques; Time; Tooth Diseases; Transcript; Twin Multiple Birth; Water; Work; acid stress; bacteriocin; biological adaptation to stress; comparative; deciduous tooth; gene function; mRNA Differential Displays; metagenomic sequencing; microbial; microbiome; novel; oral microbiome; public health relevance; sugar; transcriptomics; treatment strategy

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.

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有着良好的联系。我们的研究致力于确定许多物种的相对丰度，这些物种包括60- 70对在关联和纵向研究中与龋齿不一致的双胞胎中的牙菌斑微生物组。使用不一致的双胞胎对龋齿的研究能力大大高于使用无关个体的类似研究。接下来，我们将通过深度宏基因组测序比较无龋和龋活性微生物组，以确定差异丰富的基因和代谢途径。最后，我们将确定差异丰富的物种，菌株和基因的功能相关性进行有针对性的元转录组学研究。将确定所有数据集的统计学显著性，这将允许广泛识别与龋齿和牙齿健康相关的物种、菌株、基因和转录物。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。 公共卫生关系：我们的项目直接致力于识别导致龋齿发生和发展的微生物。所产生的数据将使我们能够确定牙齿健康和疾病的许多诊断标志物。这项工作也可能定义龋齿的新疗法。