Caries resistance mechanisms in high-risk Indigenous children

项目总结 我们对自然机制是否会保护高危儿童免受 龋齿是由口腔中共生细菌的微生物相互作用引起的，或者是由 微生物群和牙齿，由唾液介导。长期目标是预防幼儿龋齿(ECC) 通过保护性治疗保护北美土著儿童，这些治疗可能也适用于更广泛的 人口。基于研究小组强有力的初步数据，中心假设是患有 在没有ECC的情况下，一个或多个关键驱动因素不同：i)变形链球菌的微生物产酸能力降低，或ii) 牙釉质和牙本质的性质、成分或生化指纹。此应用程序的目标是 将观察学和基础科学结合起来，从关联到测试潜在龋齿的实验 变形链球菌水平高的儿童的保护机制。这项研究的理论基础是基于斯特朗 证据：i)Rothia sp.积极控制变形链球菌的酸化，ii)牙釉质和牙本质在 两组之间的组成，无龋齿儿童牙齿中铅、镉和硫较低 与患龋齿的非患龋区相比。研究小组计划进行以下工作 三个具体目标：目标1.测试Rothia和/或其他口腔植物是否以及如何减轻龋齿 产酸菌的作用。目的2.测试牙齿特性是否以及如何调节对酸的敏感性 牙釉质和牙本质溶解。目的3.测试牙齿基质或唾液对产酸能力和空间的影响 生物膜的结构，以及从体外牙菌斑生长的生物膜的空间结构是否与 受ECC影响的儿童和CF儿童。预计这一贡献将超越单一风险，产生较高的影响 涉及微生物遗传学、生物膜组织的防龋机制的因素研究 和牙齿成分。这项拟议的研究是创新的，因为我们将重点转移到一小部分 患有高负荷变形链球菌且无龋齿病史的土著儿童使用最先进的成像技术 标准化釉质芯片上体外可控生物膜生长技术，多模式集成 牙釉质和牙本质特性、生化指纹和矿物成分分析。这一贡献 这将是重大的，因为龋齿对北美土著儿童的影响是不成比例的。之后 这个项目的成功完成，对分子相互作用和生理的新的机械见解 口腔共生菌群减少致龋性物种产酸的功能可以告知新的龋病 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.