Reconstructing early life environmental exposures using tooth biomarkers and their influence on the trajectory of the oral microbiome and oral health in childhood

使用牙齿生物标志物重建早期生活环境暴露及其对儿童口腔微生物组和口腔健康轨迹的影响

• 批准号: 10405019
• 负责人: Christina Jane Adler
• 金额: $ 60.14万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405019
• 关键词: 1 year old; 8 year old; Affect; Age; Biological; Biological Assay; Biological Markers; Birth; Chemical Exposure; Chemicals; Childhood; Clinical; Clinical Data; Conceptions; Data; Dental; Dental caries; Development; Developmental Biology; Dimensions; Disease; Elements; Endocrine; Environment; Environmental Exposure; Environmental Risk Factor; Evolution; Exposure to; Fetal Development; Foundations; Future; Genes; Genetic Risk; Goals; Health; Histologic; Hour; Human; Human Microbiome; Immune; Intervention; Joints; Life; Link; Measurement; Measures; Mediating; Metabolic; Metagenomics; Methods; Mission; Mixed Dentition; Mouth Diseases; National Institute of Dental and Craniofacial Research; Non-linear Models; Nutrient; Nutritional; Odontogenesis; Oral health; Outcome; Participant; Pathway interactions; Periodontal Diseases; Placenta; Poison; Predisposition; Prevalence; Prospective cohort; Recording of previous events; Research; Research Design; Research Support; Resources; Risk; Sampling; Second Pregnancy Trimester; Statistical Data Interpretation; Statistical Methods; Sum; System; Techniques; Technology; Testing; Third Pregnancy Trimester; Time; Tooth Diseases; Tooth structure; Toxicant exposure; Translating; Twin Multiple Birth; Twin Studies; cohort; cost effective; deciduous tooth; dysbiosis; early childhood; early life exposure; environmental chemical; experience; fetal; gut microbiome; health data; high dimensionality; improved; innovation; metabolome; metabolomics; microbial; microbiome; multidimensional data; novel; novel marker; oral microbiome; permanent tooth; population based; postnatal; prenatal; prevent; repository; response; synergism; temporal measurement; toxic metal

PROJECT SUMMARY Dysbiosis between the oral microbiome and host underpins the development of dental caries. Assembly of the oral microbiome occurs hours after birth and evolves over time in response to environmental exposures. Early life is therefore a critical window when the microbiome is particularly susceptible to environmental exposures, including nutritional and toxic chemicals. Large scale studies of the impact of early life environment exposures on microbiome trajectories and subsequent risk of pediatric caries, have been prevented due to a lack of technology to directly measure the fetal environmental exposures and lack of statistical measures to account for the high dimensional data generated by –omic assays. We propose to overcome these limitations by combining metagenomic oral microbiome data with direct measures of fetal and postnatal exposure to essential elements and toxic metals as well as metabolomics data measured from the prenatal and early childhood periods using specialized tooth-matrix biomarkers that we have developed. The long term goal is to better understand the interaction of environment and the oral microbiome, and their separate and combined effects on caries development. The overall objective of this proposal is to identify environmental exposures and critical windows during development that impact the microbiome trajectory and modify caries risk. We leverage an existing population-based prospective cohort of 500 twins in which biosamples, clinical data and supporting data have already been collected from a substantial portion of participants. Our overarching hypothesis is that environmental exposures during early life alter the acquisition and maturation of the oral microbiome, and in the background of genetic risk, mediate oral health outcomes in childhood. Guided by strong preliminary data, this hypothesis will be tested by 1) determining the association between prenatal and early postnatal exposures with the assembly and evolution of the oral microbiome and 2) determining how early life exposures and oral microbiome trajectories contribute, separately and jointly, to caries risk. The approach is innovative in its technique of measuring biomarkers of environmental exposures in temporally assigned zones of deciduous teeth to reconstruct prenatal and early postnatal histories of exposure, measurement of the oral microbiome at 5 time points to construct trajectories, application of high dimensional statistical methods and leveraging of a twin cohort to assess gene x environment x microbiome interactions. The proposed research is significant because it will identify actionable environmental risk factors for pediatric dental caries and lay the foundation for future studies that can leverage these resources to better understand the interaction between environmental exposure mixtures and microbiome trajectories and impacts on oral health.

项目摘要 口腔微生物组和宿主之间的生态失调是龋齿发展的基础。组装 口腔微生物组在出生后数小时发生，并随着时间的推移对环境暴露作出反应。早期 因此，当微生物组特别容易受到环境暴露的影响时， 包括营养和有毒化学物质。早期生命环境暴露影响的大规模研究 微生物组轨迹和随后的儿童龋齿风险，由于缺乏 直接测量胎儿环境暴露的技术，缺乏统计措施来说明 对于由组学分析产生的高维数据。我们建议通过以下方式克服这些局限性： 将宏基因组口腔微生物组数据与胎儿和出生后暴露于必需的 元素和有毒金属以及从产前和幼儿期测量的代谢组学数据 使用我们开发的专门的牙齿基质生物标志物。长期目标是更好地 了解环境和口腔微生物组的相互作用，以及它们对口腔微生物的单独和综合影响。 龋齿发展本提案的总体目标是确定环境暴露和关键 在发育过程中的窗口，影响微生物群的轨迹和修改龋齿的风险。我们利用 现有的基于人群的500对双胞胎的前瞻性队列，其中生物样本，临床数据和支持 已经从相当一部分参与者那里收集了数据。我们的首要假设是 早期生活中的环境暴露改变了口腔微生物组的获得和成熟， 遗传风险背景，介导儿童口腔健康结果。在强大的初步数据指导下， 将通过以下方式检验假设：1）确定产前和产后早期暴露之间的关联 与口腔微生物组的组装和进化有关，以及2）确定早期生活暴露和口腔 微生物组轨迹单独和共同地导致龋齿风险。该方法具有创新性， 在时间上指定的落叶层中测量环境暴露的生物标志物的技术 牙齿重建产前和出生后早期的接触史，口腔微生物组的测量， 5个时间点构建轨迹，应用高维统计方法并利用 双胞胎队列评估基因x环境x微生物组相互作用。所提出的研究是有意义的 因为它将确定儿童龋齿的可操作环境风险因素，并为 未来的研究可以利用这些资源来更好地了解环境之间的相互作用 暴露混合物和微生物组轨迹以及对口腔健康的影响。