Dental caries is the most common chronic disease in children that causes negative effects on their health, development, and well-being. Early preventive interventions are key to reduce early childhood caries prevalence. An efficient strategy is to provide risk-based targeted prevention; however, this requires an accurate caries risk predictor, which is still lacking for infants before caries onset. We aimed to develop a caries prediction model based on the salivary microbiome of caries-free 1-y-old children. Using a nested case-control design within a prospective cohort study, we selected 30 children based on their caries status at 1-y follow-up (at 2 y old): 10 children who remained caries-free, 10 who developed noncavitated caries, and 10 who developed cavitated caries. Saliva samples collected at baseline before caries onset were analyzed through 16S rRNA gene sequencing. The results of β diversity analysis showed a significant difference in salivary microbiome composition between children who remained caries-free and those who developed cavitated caries at 2 y old (analysis of similarities, Benjamini-Hochberg corrected, P = 0.042). The relative abundance of Prevotella nanceiensis, Leptotrichia sp. HMT 215, Prevotella melaninogenica, and Campylobacter concisus in children who remained caries-free was significantly higher than in children who developed cavitated caries (Wilcoxon rank sum test, P = 0.024, 0.040, 0.049, and 0.049, respectively). These taxa were also identified as biomarkers for children who remained caries-free (linear discriminant analysis effect size, linear discriminant analysis score = 3.69, 3.74, 3.53, and 3.46). A machine learning model based on these 4 species distinguished between 1-y-old children who did and did not develop cavitated caries at 2 y old, with an accuracy of 80%, sensitivity of 80%, and specificity of 80% (area under the curve, 0.8; 95% CI, 44.4 to 97.5). Our findings suggest that these salivary microbial biomarkers could assist in predicting future caries in caries-free 1-y-old children and, upon validation, are promising for development into an adjunctive tool for caries risk prediction for prevention and monitoring.
Keywords: biomarkers; dental caries; infant; machine learning; microbiota; saliva.