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: 10624433
• 负责人: Christina Jane Adler
• 金额: $ 71.62万
• 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/10624433
• 关键词: 1 year old; 8 year old; Affect; Age; Biological; Biological Assay; Biological Markers; Birth; Calibration; 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; Linear Models; 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营养不良是龋齿的发展。组装 口服微生物组在出生后数小时发生，并随着环境暴露而随着时间的流逝而演变。早期的 因此，当微生物组特别容易受到环境暴露时，生活是一个关键的窗口， 包括营养和有毒化学物质。大规模研究早期生活环境的影响 关于微生物组轨迹和随后的小儿龋齿风险，由于缺乏 直接测量胎儿环境暴露和缺乏统计测量的技术 对于由–omic分析产生的高维数据。我们建议通过 将宏基因组学微生物组数据与胎儿和产后暴露于必需品的直接测量结合 元素和有毒金属以及从产前和幼儿测量的代谢组学数据 使用我们已经开发的专门牙齿质体生物标志物的时期。长期目标是更好 了解环境与口服微生物组的相互作用，以及它们对 进行发展。该提案的总体目的是确定环境暴露和关键 开发过程中的窗户会影响微生物组轨迹并改变汽车风险。我们利用一个 现有的基于人群的前瞻性队列500个双胞胎，其中生物样本，临床数据和支持 数据已经是从大部分参与者中收集的。我们的总体假设是 早年的环境暴露会改变口服微生物组的获取和成熟，在 遗传风险的背景，介导童年的口腔健康结果。在强大的初步数据的指导下， 假设将通过1）确定产前和早期产后暴露之间的关联 随着口服微生物组的组装和演变以及2）确定早期寿命的暴露方式和口腔 微生物组轨迹分别和共同贡献了风险。这种方法是创新的 测量临时分配的落叶区域中环境暴露生物标志物的技术 牙齿以重建产前和早期暴露后历史，测量口腔微生物组 构建轨迹的5个时间点，高维统计方法的应用和利用 双胞胎队列评估基因X环境X微生物组相互作用。拟议的研究很重要 因为它将确定儿科牙科可行的环境风险因素，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。

项目成果

Development of the oral resistome during the first decade of life.

• DOI: 10.1038/s41467-023-36781-w
• 发表时间: 2023-03-09
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Sukumar S;Wang F;Simpson CA;Willet CE;Chew T;Hughes TE;Bockmann MR;Sadsad R;Martin FE;Lydecker HW;Browne GV;Davis KM;Bui M;Martinez E;Adler CJ
• 通讯作者: Adler CJ

How does the early life environment influence the oral microbiome and determine oral health outcomes in childhood?

• DOI: 10.1002/bies.202000314
• 发表时间: 2021-09
• 期刊: BIOESSAYS
• 影响因子: 4
• 作者: Adler, Christina Jane;Cao, Kim-Anh Le;Hughes, Toby;Kumar, Piyush;Austin, Christine
• 通讯作者: Austin, Christine