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.

项目总结

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