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: 10033272
• 负责人: Christina Jane Adler
• 金额: $ 64.37万
• 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/10033272
• 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; 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.

项目总结 口腔微生物群和宿主之间的失调是龋齿发生的基础。装配的 口腔微生物组在出生后几个小时发生，并随着时间的推移而进化，以应对环境暴露。早些时候 因此，当微生物群特别容易受到环境暴露时，生命是一个关键的窗口， 包括营养和有毒化学物质。早期生活环境暴露影响的大规模研究 对微生物组轨迹和随后的儿童龋病风险的影响，由于缺乏 直接测量胎儿环境暴露的技术和缺乏统计方法来说明 用于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限制 将元基因组口腔微生物组数据与胎儿和出生后接触必需物质的直接测量相结合 元素和有毒金属以及从产前和儿童早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记物。我们的长期目标是更好地 了解环境和口腔微生物群的相互作用，以及它们对 龋齿的发展。这项提案的总体目标是确定环境暴露和关键 在发育过程中影响微生物群轨迹和修改龋齿风险的窗口。我们利用 现有的基于人群的500对双胞胎前瞻性队列，其中包括生物样本、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。我们最重要的假设是 生命早期的环境暴露改变了口腔微生物群的获取和成熟，在 遗传风险背景，调节儿童口腔健康结果。在强劲的初步数据指引下，这 假设将通过1)确定出生前和出生后早期接触之间的联系来检验 与口腔微生物组的组装和进化以及2)决定早期生命暴露和口腔 微生物群的轨迹分别和联合地增加了龋病风险。该方法的创新之处在于其 在时间上指定的落叶区域测量环境暴露的生物标志物的技术 用于重建出生前和出生后早期暴露史的牙齿，口腔微生物组的测量 5个时间点以构建轨迹，应用高维统计方法并利用 评估基因x环境x微生物群相互作用的双生子队列。这项拟议的研究具有重要意义 因为它将确定可操作的儿童龋齿环境危险因素，并为 未来的研究可以利用这些资源来更好地理解环境和环境之间的相互作用 接触混合物和微生物群的轨迹及其对口腔健康的影响。