Caries resistance mechanisms in high-risk Indigenous children

高危原住民儿童的防龋机制

• 批准号: 10639704
• 负责人: Felicitas B Bidlack
• 金额: $ 82.99万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-04 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639704
• 关键词: Acids; Address; Affect; Aluminum; American; Bacteria; Basic Science; Binding; Biochemical; Cadmium; Carbohydrates; Cells; Child; Classification; Data; Dental Enamel; Dental Plaque; Dental caries; Dentin; Dimensions; Elements; Epidemiology; Etiology; Exclusion; Fermentation; Fingerprint; Gene Expression; Genes; Genomics; Goals; Grant; Growth; Hardness; Histology; Hybrids; Image; Imaging Techniques; In Vitro; Indigenous; Indigenous American; Knowledge; Lead; Legal patent; Mechanics; Methods; Microbe; Microbial Biofilms; Microbial Genetics; Minerals; Minority; Modeling; Molecular; Molecular Epidemiology; Oral; Oral cavity; Oral health; Participant; Physiological; Population; Predisposition; Prevention strategy; Preventive; Production; Property; Proteins; Public Health; Recording of previous events; Reproducibility; Research; Research Design; Resistance; Risk; Risk Factors; Saliva; Salivary; Sampling; Science; Signal Transduction; Standardization; Statistical Data Interpretation; Streptococcus mutans; Structure; Sulfur; Taxon; Testing; Therapeutic; Time; Tissues; Tooth structure; active control; bacterial genetics; cariogenic bacteria; commensal bacteria; crystallinity; density; early childhood; experimental study; high risk; high risk population; innovation; insight; microbial; microbiome; microorganism interaction; mineralization; multidimensional data; multimodality; novel; oral bacteria; oral commensal; oral streptococci; polymicrobial biofilm; population based; prevent; protective factors; rRNA Genes; resistance mechanism; saliva mediated; socioeconomic disparity; transcriptomics

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.

项目概要 我们对自然机制是否能保护高危儿童免受感染的认识存在根本性差距 龋齿是由口腔内共生细菌的微生物相互作用引起的，或者是由 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（ECC）。 北美土著儿童通过保护性治疗也可能适用于更广泛的地区 基于研究小组强有力的初步数据，中心假设是儿童患有以下疾病。 与没有 ECC 的情况在一个或多个关键驱动因素上存在差异：i) 微生物降低变形链球菌的产酸性，或 ii) 本申请的目的是确定牙釉质和牙本质的特性、成分或生化指纹。 整合观察和基础科学，从关联到测试潜在龋齿的实验 具有高水平变形链球菌的儿童的保护机制 该研究的基本原理是基于强有力的。 有证据表明，i) Rothia sp 主动控制变形链球菌酸生成，ii) 牙釉质和牙本质存在差异。 两组之间的成分比较，无龋齿儿童牙齿中的铅、镉和硫含量较低 与受龋齿影响的牙齿的未受影响区域相比，研究小组计划进行以下研究。 三个具体目标： 目标 1. 测试 Rothia 和/或其他口腔物种是否以及如何减轻致龋性 目标 2. 测试牙齿特性是否以及如何调节对酸的敏感性。 目标 3. 测试牙齿基质或唾液如何影响酸原性和空间。 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存在差异 预计该捐款将超越单一风险，对受 ECC 影响的儿童和 CF 儿童产生巨大影响。 因素研究，调查涉及微生物遗传学、生物膜组织的防龋机制 所提出的研究是创新的，因为我们将重点转移到了一小部分。 变形链球菌含量高且无龋病史的土著儿童使用最先进的成像技术 标准化牙釉质芯片上体外控制生物膜生长技术，并集成多模式 分析牙釉质和牙本质特性、生化指纹和矿物质成分。 将会很重要，因为龋齿对北美土著儿童的影响不成比例。 该项目的成功完成，对分子相互作用和生理学有了新的机制见解 口腔共生菌群减少致龋物种酸产生的功能可以为新的龋齿提供信息 预防性治疗策略。