Caries resistance mechanisms in high-risk Indigenous children

项目摘要 我们对自然机制是否能保护高危儿童免受 龋齿和产生的微生物相互作用的细菌在口腔中，或从相互作用， 微生物组和牙齿，由唾液介导。长期目标是预防儿童早期龋齿， 北美土著儿童通过保护性治疗，也可能适用于更广泛的 人口根据研究小组的初步数据，中心假设是， 和没有ECC的情况下的差异在于一个或多个关键驱动因素：i）微生物降低的S.变异体，或ii） 牙釉质和牙本质特性、成分或生化指纹。本申请的目的是 综合观察和基础科学，从协会到测试潜在龋齿的实验 高水平S.变异人该研究的基本原理是基于强大的 证据表明i）Rothia sp.主动控制S.变形菌产酸，和ii）釉质和牙本质不同， 两组之间的组成，与铅，镉，硫较低的牙齿，从无龋儿童 与未受龋齿影响的牙齿区域相比。研究小组计划进行以下工作 三个具体目标：目标1。测试罗西亚和/或其他口腔物种是否以及如何减轻致龋性 产酸细菌的影响。目标2.测试牙齿特性是否以及如何调节对酸的敏感性 牙釉质和牙本质的溶解。目标3。测试牙齿基质或唾液如何影响产酸性和空间 生物膜的结构，以及从离体牙菌斑生长的生物膜的空间结构是否在 受幼儿保育和CF影响的儿童。预计捐款将通过超越单一风险而产生巨大影响 因素研究，以调查涉及微生物遗传学、生物膜组织的龋齿保护机制 和牙齿组成。拟议的研究是创新的，因为我们把重点转移到小部分的 原住民儿童高负荷的S。无龋齿史，使用最先进的成像技术 体外控制生物膜在标准化釉质芯片上生长的技术， 分析牙釉质和牙本质特性、生化指纹和矿物成分。这一贡献 将是重要的，因为龋齿会影响北美土著儿童。后 该项目的成功完成，对分子相互作用和生理学的新的机理见解， 口腔内植物群减少致龋物种产酸的功能可告知新的龋齿 预防性治疗策略。

PROJECT SUMMARY There is a fundamental gap in our knowledge whether natural mechanisms protect high-risk children from caries and arise from microbial interactions of commensal bacteria in the oral cavity, or from the interplay of microbiome and tooth, mediated by saliva. The long-term goal is to prevent early childhood caries (ECC) in North American Indigenous children through protective treatments that may also be applicable in the broader population. The central hypothesis, based on the research team’s strong preliminary data, is that children with and without ECC differ in one or more key drivers: i) microbially reduced acidogenicity of S. mutans, or ii) enamel and dentin properties, composition, or biochemical fingerprint. The objective in this application is to integrate observational and basic science, from associations to experiments that test underlying caries protection mechanisms in children with high levels of S. mutans. The study rationale is based on strong evidence that i) Rothia sp. actively control S. mutans acidogenesis, and ii) enamel and dentin differ in composition between the two groups, with lead, cadmium, and sulfur lower in teeth from caries-free children compared with the unaffected region of caries-affected teeth. The research team plans to pursue the following three Specific Aims: Aim 1. Test whether and how Rothia and/or other oral species may mitigate the cariogenic effects of acidogenic bacteria. Aim 2. Test whether and how tooth properties modulate the susceptibility to acid dissolution of enamel and dentin. Aim 3. Test how tooth substrate or saliva affect acidogenicity and spatial structure of biofilms, and whether spatial structure of biofilms grown from ex vivo dental plaque differs between ECC-affected and CF children. The contribution is expected to achieve high impact by going beyond single-risk factor studies to investigate caries-protective mechanisms involving microbial genetics, biofilm organization and tooth composition. The proposed research is innovative, because we shift focus to the small percentage of Indigenous children with high loads of S. mutans and without caries history, use state-of-the art imaging techniques of in vitro controlled biofilm growth on standardized enamel chips, and integrate multimodal analyses of enamel and dentin properties, biochemical fingerprint, and mineral composition. This contribution will be significant because dental caries disproportionally affects North American Indigenous children. After successful completion of this project, new mechanistic insights into molecular interactions and physiological functions of commensal oral flora to reduce acid production in cariogenic species can inform new caries preventive therapeutic strategies.