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.

项目摘要 我们知道自然机制是否保护高风险儿童免受 龋齿和来自口腔中共生细菌的微生物相互作用，或者是由 微生物组和牙齿，由唾液介导。长期目标是防止幼儿园（ECC） 北美土著儿童通过保护性疗法也可能适用于广泛 人口。基于研究团队的强大初步数据的中心假设是 并且在一个或多个关键驱动因素中没有ECC不同：i）微生物降低了突变链球菌的酸性，或II） 搪瓷和牙本质特性，成分或生化指纹。此应用程序的目的是 从关联到测试基础汽车的实验，综合观察和基础科学 较高链球菌的儿童的保护机制。研究理由是基于强大的 证据i）Rothia sp。积极控制链球菌的酸生成，ii）牙釉质和牙本质不同 两组之间的组成，带有铅，镉和硫的牙齿中的牙齿较低 与不受龋齿影响的牙齿的不受影响的区域相比。研究小组计划追求以下 三个特定目的：目标1。测试Rothia和/或其他口腔物种是否可以减轻致癌 酸性细菌的作用。目标2。测试牙齿特性是否调节酸的易感性 搪瓷和牙本质的溶解。目标3。测试牙齿基材或唾液如何影响酸性和空间 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有所不同 受ECC影响和CF儿童。预计该贡献将通过超越单风险来实现高影响力 研究涉及微生物遗传学的汽车保护机制，生物膜组织 和牙齿成分。拟议的研究具有创新性，因为我们将重点转移到了一小部分 具有高负载的S. mutan且没有历史的土著儿童，使用最先进的成像 标准化搪瓷芯片上体外控制生物膜生长的技术，并集成多模式 搪瓷和牙本质特性，生化指纹和矿物质成分的分析。这个贡献 将是重要的，因为龋齿不成比例地影响北美土著儿童。后 成功完成该项目，对分子相互作用和生理的新机械见解 共生口服菌群的功能减少致癌物种的酸产生，可以告知新的龋齿 预防性治疗策略。