Deep Saliva Proteomics Elucidating the Pathogenesis of Early Childhood Caries and Identifying Biomarkers for Early Prediction

Early childhood caries (ECC) significantly impacts the physical and mental health of children. Saliva stands as a critical model for investigating the pathogenesis of caries disease since it reflects both host and microbial dynamics. However, the specific contributions of salivary host factors to ECC have not been fully understood. In this study, we monitored a prospective cohort of 3-4 year-old healthy children for 12 months, who either stayed caries-free or developed caries. Deep quantitative proteomics analysis of saliva was conducted at both recruitment and end point of the cohort to investigate the molecular mechanisms underlying ECC etiology and identify potential biomarkers for caries prediction. Proteomics analysis identified a total of 2873 proteins and revealed involvement of immune response, dental structure repair, and regeneration, as well as interactions with microorganisms during caries pathogenesis. Characteristic salivary proteins were identified in caries-susceptible children prior to caries development. An ECC prediction panel of proteins keratin 3 (KRT3) and mucin 21 (MUC21) was established and further validated through another independent cohort. This study illuminated the role of the complex salivary microenvironment in caries etiology and offered a prognostic tool for early ECC prediction, thus facilitating the precise prevention and control of ECC to ultimately reduce its incidence.