Prediction of future caries in toddlers via salivary microbiome: A 1-year longitudinal study

Abstract

Dental caries in children is the most common chronic oral disease that could disturb their quality of life including their development. Early prevention is a key approach to reducing the prevalence of early childhood caries. However, a reliable caries predictor, as an essential tool for targeted prevention that is important to this approach, is still lacking for infants before caries onset. Therefore, we aimed to develop the caries risk prediction model based on the salivary microbiome of caries-free 1-year-old children to predict caries onset at 1-year follow-up. Using a nested case-control design within a prospective cohort study, 30 saliva samples, collected at a baseline time point, were selected based on sufficient sample quantity and caries status when children were 2-year-old: 10 children who developed non-cavitated caries lesions, 10 who developed cavitated caries lesions, and 10 who remained caries-free then 16S rRNA gene sequencing was performed. The salivary microbiota of the children who remained caries-free was significantly different when compared with those who developed cavitated caries lesions (unweighted UniFrac, ANOSIM, Benjamini-Hochberg corrected, P = 0.042). The relative abundance of Prevotella nanceiensis, Leptotrichia sp. HMT 215, Prevotella melaninogenica, and Campylobacter concisus were significantly higher in the children who remained caries-free compared with those who developed cavitated caries lesions (Wilcoxon rank-sum test, P = 0.024, 0.040, 0.049, and 0.049, respectively) and were identified as biomarkers for the children who remained caries-free (LEfSe, LDA score = 3.69, 3.74, 3.52, and 3.46, respectively). Caries prediction model generated by machine learning based on these 4 biomarkers differentiated the 1-year-old children between those who did and did not develop cavitated caries lesion at 2-year-old with an accuracy of 80%, sensitivity of 80%, and specificity of 80% (AUC, 0.8; 95% CI, 44.4-97.5). These findings suggest that the salivary microbiome of caries-free 1-year-old children could predict future caries onset in infants that could further develop into a promising caries predictor for targeted prevention.