Probiotics for Prevention of Early Childhood Caries

项目摘要 2018年，我们开始招募1至3岁的幼儿参加一项旨在调查 龋齿诊断前口腔微生物组的变化。我们纳入了“传统”的衡量标准 (变形链球菌；MS)和‘当代’(念珠菌)致龋菌，但主要集中在非MS 低pH链球菌。这项研究仍将以比最初更可靠的数据集完成 估计是由于自然减员低于预期。然而，与Covid相关的延误推迟了 在资助期正式结束之前完成研究。对于这一竞争性续订申请， 我们检查了数据的当前状态。正如预期的那样，我们还不能就这一角色得出结论 非MS低pH链球菌在龋病发生中的作用然而，我们遇到了一个意想不到但令人兴奋的 发现：轻度嗜酸性链球菌--我们将其命名为高pH值菌株--主要是 在18个月内保持无龋齿的受试者中发现，包括一名无龋齿的受试者 受试者有患龋齿的特征。这种高pH值菌株的分布类似于我们 之前观察到的是一群年龄较大的儿童。来自后一组的几个菌株被评估为 具有良好的益生菌特性，四个菌株脱颖而出。2021-2026 NIDCR的战略重点3 战略规划是“加快翻译研究”。。。转变为减少健康差距的做法。 这款竞争性续订申请就是为此而设计的。我们计划发展我们的益生菌库 通过彻底分析它们的益生菌特性，测试它们的安全性，以及 开发适合年龄和文化敏感的新分娩方式，为未来的临床做准备 在历史上经历过龋病健康差异的人群中减少龋齿发病率的试验。具体的 这项提议的目的是1)开发一种具有互补特性和安全性的益生菌菌株的鸡尾酒 在细胞培养和动物模型中进行测试；以及2)开发最具吸引力和有效的递送方式 不同的人群和年龄较小的儿童。目前，益生菌的商业选择很少。 专门为促进口腔健康而挑选的。拟议目标的完成将大大扩大 促进健康的口腔益生菌系列，并为测试一种全新的方法奠定了基础 缩小健康差距。

Project Summary In 2018, we began enrolling young children, ages 1 to 3, in a longitudinal study designed to investigate changes in the oral microbiome in advance of a caries diagnosis. We included measures of ‘traditional’ (mutans streptococci; MS) and ‘contemporary’ (Candida) cariogens but centered our main focus on non-MS low pH streptococci. This study remains on track for completion with a more robust data set than originally estimated due to lower-than-expected attrition. However, Covid-related delays have pushed back the completion of the study until after the official end of the grant period. For this competitive renewal application, we examined the current state of the data. As expected, we could not yet draw a conclusion regarding the role of non-MS low pH streptococci in caries development. However, we came upon an unexpected but exciting discovery: strains of mildly acidogenic streptococci – that we designated ‘high pH’ strains – were predominantly found in subjects who remained caries-free during their eighteen months in the study, including one caries-free subject who otherwise exhibited a cariogenic profile. This distribution of high pH strains is similar to what we previously observed with a cohort of older children. Several strains from this latter group were evaluated for desirable probiotic properties and four strains stood out. Strategic Priority #3 from the 2021-2026 NIDCR Strategic Plan is to “accelerate the translation of research . . . into practices that reduce health disparities.” This competitive renewal application is designed to do that. We propose to develop our pool of probiotic candidates by thoroughly analyzing them for their breadth of probiotic qualities, testing their safety, and developing novel means of age-appropriate and culturally sensitive delivery in preparation for a future clinical trial to reduce caries incidence in populations that historically experience caries health disparities. The specific aims of this proposal are to 1) Develop a cocktail of probiotic strains with complementary properties and safety test in cell culture and animal models; and 2) Develop the most attractive and effective means of delivery for diverse populations and children of young age. At present, there are few commercial options for probiotics specifically selected to promote oral health. Completion of the proposed aims will profoundly expand the repertoire of health-promoting oral probiotics and set the stage for testing an entirely novel approach for reducing health disparities.