The Impact of Bacterial–Fungal Interactions on Childhood Caries Pathogenesis

Caries is the most prevalent chronic disease affecting oral health in preschool children. In this 12-month prospective cohort study of 3-4-year-olds, we investigated the community-level bacterial-fungal interkingdom interactome and its role in cariogenic microenvironments, using 16S rRNA gene (bacterial) sequencing and ITS2 gene (fungal) sequencing of unstimulated saliva. Longitudinal analysis identified 19 key bacterial and fungal species that were associated with both caries progression and clinical features. Salivary bacteria <i>Desulfovibrio</i>, <i>Bacteroides heparinolyticus</i>, <i>Alloprevotella</i>, <i>Anaerobiospirillum</i>, and fungus <i>Candida tropicalis</i> not only showed altered abundances during caries development but also correlated with severity of caries, establishing diagnostic microbial signatures for caries prediction. The salivary mycobiome exhibited highly active and complex intra-network interactions in the caries-active state, suggesting that fungal networks may drive the broader community-wide microbiota interaction network in the caries state. Metabolic profiling further revealed distinct pathway shifts before and after caries onset. The findings demonstrate that caries progression follows ecological succession governed by cross-domain interactions. This study highlighted the fungal network's important role in driving dysbiosis, advancing the current understanding of early childhood caries beyond bacterial-centric models, and also highlighted fungi not only as modulators but as active contributors to cariogenesis, which could guide future antimicrobial strategies.