Environmental and Genetic Factors Contributing to the Development of the Early-Life Oral Microbiome and its Influence on Early Childhood Caries

项目摘要 发生在6岁以下儿童乳牙期或儿童早期的龋病 龋病(ECC)影响着超过五分之一的美国2-5岁儿童。ECC是一个多因素的 疾病：口腔微生物群、宿主行为和遗传因素影响龋病风险。 预防ECC可以改善口腔和全身健康，并减轻整个社区的医疗负担 生命历程。通过更好地了解ECC的因果机制，我们可能能够改进 依靠预防和干预努力。我们将使用已经收集的人类基因型别， 唾液和牙菌斑微生物组，以及来自 参加阿巴拉契亚口腔健康研究中心第二组的儿童： 1)比较用于表征发育中的唾液微生物组的数据简化方法， 2)评估早期接触、早期口腔微生物群和 ECC，以及 3)宿主基因对口腔微生物群与ECC关系的影响修正试验 龋齿风险。 拟议的研究有可能确定环境和微生物因素， 鼓励或抑制致龋性口腔微生物群的发展，并确定 对口腔微生物组进行干预的人类遗传亚群 特别有效。 有了这个研究方案和培训计划，申请者将获得纵向分析的技能 高维数据、微生物和人类遗传数据的处理以及在以下方面获得专业知识 龋病的多因素病因学。拟议的培训将支持申请人的 长期目标是成为一名独立研究人员，专注于 微生物、行为和人类遗传因素在口腔疾病发展中的作用。 该项目与NIDCR 2030的精准健康、自我治疗和口腔治疗目标一致 健康总体健康。

Project Abstract Caries that occur in the primary dentition of children aged under 6 years, or early childhood caries (ECC), affect more than one-fifth of US children aged 2-5. ECC is a multifactorial disease: the oral microbiome, host behaviors and genetic factors influence caries risk. Preventing ECC can improve oral and systemic health and reduce healthcare burden across the life course. By better understanding the causal mechanisms of ECC we may be able to improve upon prevention and intervention efforts. We will use already collected human genotypes, salivary and dental plaque microbiome, and sociodemographic and behavioral data from children participating in the Center for Oral Health Research in Appalachia cohort 2 to: 1) compare data reduction methods for characterizing the developing salivary microbiome, 2) assess the relationships between early-life exposures, the early-life oral microbiome and ECC, and 3) test for effect modification of the oral microbiomes’ relationship with ECC by host genetic caries risk. The proposed study has the potential to identify environmental and microbial factors which encourage or discourage the development of a cariogenic oral microbiome and to identify human genetic subpopulations for whom interventions on the oral microbiome may be especially effective. With this research proposal and training plan the applicant will gain skills in longitudinal analysis of high-dimensional data, processing of microbial and human genetic data and gain expertise in the multifactorial etiology of dental caries. The proposed training will support the applicant’s long-term goal of becoming an independent researcher focusing on the interplay between microbial, behavioral and human genetic factors in the development of oral disease. This project is consistent with NIDCR 2030 goals of Precision Health, Autotherapies and Oral Health + Overall Health.