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Longitudinal Analysis of Low pH Streptococci and Plaque Microbiome in Early Childhood Caries

儿童早期龋齿中低 pH 链球菌和菌斑微生物组的纵向分析

基本信息

批准号：
10388260
负责人：
Jeffrey A Banas
金额：
$ 53.83万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10388260
关键词：
Acid-Base Equilibrium Age Area Bacteria Bioinformatics Carbohydrates Child Clinical Data Data Analyses Dental Enamel Dental Hygiene Dental Plaque Dental caries Development Ecology Elements Epidemiology Equilibrium Etiology Experimental Designs Genes Genomics Grouping Health Integration Host Factors Iowa Lead Left Lesion Literature Longitudinal Studies Minority Nutritional Odontogenesis Oral cavity Organism Outcome Pathology Pattern Pediatric Dentistry Phenotype Population Prevention Property Prospective Studies Research Research Priority Risk Risk Assessment Role Sampling Scoring Method Site Streptococcus Streptococcus Viridans Group Streptococcus anginosus Streptococcus gordonii Streptococcus mitis Streptococcus mutans Streptococcus oralis Subgroup Taxonomy Time Uncertainty United States National Institutes of Health Universities aged alkalinity base dietary early childhood exhaust health disparity high risk high risk population implementation science improved innovation longitudinal analysis member microbial microbiome microbiome composition novel novel strategies oral microbiome oral plaque oral streptococci pediatric department prospective sound

项目摘要

ABSTRACT The microbial etiology of dental caries remains a subject of debate with considerable differences of opinion regarding the relative contributions of specific species or classes of bacteria. The `low pH streptococci' is a designation given to atypical, highly acidogenic strains of oral streptococci originally thought to belong to the primary plaque colonizing species S. oralis, S. mitis, S. gordonii, and S. anginosus. This sub-group of streptococci is proposed to have considerable cariogenic potential, perhaps preceding, augmenting or even overshadowing the contribution of the mutans streptococci (MS). However, assessing the role of the low pH strep is not straightforward. Accurate assignment of species among the viridans streptococci is a challenge, and the low pH phenotype cannot be ascertained by the gene-based strategies routinely employed in non-culture based studies of the oral microbiome. In this application we propose a unique prospective study that combines state-of-the-art bioinformatics with phenotypic analyses of low pH phenotypes to track changes in the plaque microbiome, with a specific focus on the MS and non-MS low pH streptococci, as caries develop in children at high risk for early childhood caries. Specifically, our objectives are to determine if there is ascendancy of non- MS low pH streptococci within the plaque oral microbiome with potential shifts in composition of other organisms during the transition from a sound enamel site to a carious enamel site. In addition, we propose a novel and exciting approach of categorizing low pH streptococci based on their potential to produce alkaline products. We believe that gaining a more comprehensive assessment of the low pH streptococcal species or taxa, and our novel grouping of these organisms based on alkaline-producing phenotypes, as part of our determination of the plaque microbiome composition has the potential to make significant contributions to implementation science. To meet our objectives we propose the following aims: 1) Conduct an 18-month longitudinal study on high-caries risk children aged 1-3 to determine changes in the overall plaque microbiome preceding caries development, with a focus on the non-MS low pH streptococci; and 2) Use genomic sequencing to assign species identity or taxonomical relatedness to the non-MS low pH streptococci recovered in Aim 1. By coalescing and analyzing the data from the microbiome and low pH streptococci as caries develop we will define patterns or drivers of caries or health that may provide a basis for advances in implementation science.

摘要龋齿的微生物病因学仍然是一个争论的主题，关于特定细菌物种或类别的相对贡献的意见。“低pH链球菌” 是一种给予非典型的、高度产酸的口腔链球菌菌株的名称，最初被认为属于主要噬菌斑定殖种S. oralis，S. mitis、细叶山蚂蝗S. gordonii和S.心绞痛这一小组链球菌被认为具有相当大的致龋潜力，可能在致龋之前、增强致龋甚至掩盖了变形链球菌（MS）的贡献。然而，评估低pH值的作用链球菌并不简单。草绿色链球菌之间的物种的准确分配是一个挑战，低pH表型不能通过非培养中常规采用的基于基因的策略来确定基于口腔微生物组的研究。在本申请中，我们提出了一项独特的前瞻性研究，最先进的生物信息学，对低pH表型进行表型分析，以跟踪菌斑的变化微生物组，特别关注MS和非MS低pH链球菌，因为儿童龋齿的发展儿童早期龋齿风险高。具体来说，我们的目标是确定是否存在非- 菌斑口腔微生物组内的MS低pH链球菌，其他微生物的组成可能发生变化在从健康的釉质部位到龋坏的釉质部位的过渡期间。此外，我们还提出了一个新的和一种令人兴奋的方法，根据它们产生碱性产物的潜力对低pH值链球菌进行分类。我们我相信，获得一个更全面的评估低pH值链球菌物种或类群，我们的基于产碱表型对这些生物进行新的分组，作为我们确定牙菌斑微生物组组成具有为实施科学做出重大贡献的潜力。为了达到我们的目标，我们提出了以下目标：1）对高龋进行为期18个月的纵向研究 1-3岁的风险儿童，以确定龋齿发展之前整体菌斑微生物组的变化，重点关注非MS低pH链球菌;和2）使用基因组测序来指定物种身份或与目标1中回收的非MS低pH链球菌的分类学相关性。通过整合和分析微生物群系和低pH链球菌的数据作为龋齿的发展，我们将定义模式或驱动因素，龋齿或健康，可以提供实施科学进步的基础。