Integrated Multi-Omics Reveals Caries Mechanisms In Preschoolers

Preschool caries, linked to oral microbiome dysbiosis, lacks age-specific prevention. By applying integrated multi-omics, we unravel age-specific ecological-metabolic networks driving caries pathogenesis, revealing microbe-metabolite interactions as targets for ecological modulation via metabolic interventions Supragingival plaque samples were collected from 80 children aged 3-5 years (40 caries-active and 40 caries-free) stratified into four groups (n=20 each) by age and caries status. Full-length 16S rRNA sequencing analyzed species-level microbial composition. Untargeted metabolomics (LC-MS/MS) was performed on 40 samples. Spearman correlation identified microbe-metabolite interactions. Caries-active children exhibited enriched Prevotella, Veillonella, and Selenomonas, while caries-free groups showed Neisseria and Haemophilus dominance. β-diversity indicated caries status as the primary driver of microbial divergence. Age-specific patterns emerged: caries-active 3-year-olds harbored Megasphaera and Corynebacterium, whereas 5-year-olds demonstrated increased Lactobacillus and Fusobacterium. Metabolomics identified 617 differentially expressed metabolites . Caries-active plaques displayed activated amino acid metabolismand glycolysis, while caries-free samples showed active glycerophospholipid metabolism. Microbial-metabolite networks revealed strong positive correlations between cariogenic genera (e.g., Lactobacillus) and acidic metabolites (L-glutamate, Ala-Ala). Health-associated genera (e.g., Gemella) correlated with protective metabolites like xylitol (ρ=0.79). Preschool caries exhibits age-dependent microbial signatures, yet caries status remains the dominant ecological determinant. Key metabolic pathways converge on D-amino acid metabolism and glycolysis, suggesting their pivotal roles in cariogenesis. Microbe-metabolite interaction networks highlight potential therapeutic targets for modulating ecological balance through metabolic interventions.