Probiotics for Prevention of Early Childhood Caries

项目摘要 2018年，我们开始招募1至3岁的幼儿参加一项纵向研究， 在龋齿诊断之前口腔微生物组的变化。我们包括了“传统”的措施 （变形链球菌; MS）和“当代”（念珠菌）致龋，但我们的主要重点是非MS 低pH链球菌。这项研究仍在按计划完成，数据集比最初更可靠 由于自然减员低于预期，然而，与Covid相关的延迟推迟了 研究结束后，直到补助金期限正式结束。对于此竞争性续约申请， 我们检查了数据的当前状态。正如预期的那样，我们还不能就这一作用得出结论。 非MS低pH链球菌在龋病发展中的作用。然而，我们遇到了一个意想不到的，但令人兴奋的 发现：温和产酸链球菌菌株-我们指定为“高pH”菌株-主要是 在研究的18个月内保持无龋的受试者中发现， 受试者表现出致龋特征。高pH菌株的这种分布与我们所知的相似。 之前在一组年龄较大的儿童中观察到。对来自后一组的几种菌株进行了评价， 理想的益生菌特性，四种菌株脱颖而出。2021-2026年NIDCR战略优先事项#3 战略计划是“加快研究成果的转化。. .减少健康差距的实践。” 这种竞争性的更新应用程序旨在做到这一点。我们建议开发我们的益生菌池 通过彻底分析候选人的益生菌质量范围，测试其安全性， 开发适合年龄和文化敏感的新方法，为未来的临床 在历史上经历过龋齿健康差异的人群中进行降低龋齿发病率的试验。具体 该提案的目的是1）开发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）开发最有吸引力和最有效的递送手段， 不同的人群和年轻的孩子。目前，益生菌的商业选择很少 专门用于促进口腔健康。实现拟议目标将大大扩大 促进健康的口服益生菌的剧目，并为测试一种全新的方法， 减少健康差距。

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.