Probiotics for Prevention of Early Childhood Caries

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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.