Ecological succession in the oral microbiome drives caries pathogenesis: a shift from antagonistic to synergistic cross-kingdom networks

Background Severe early childhood caries (S-ECC) is driven by oral ecosystem dysbiosis. However, the coordinated roles and dynamic interactions between bacterial and fungal communities during disease progression remain largely unclear.Objective To characterize the spatiotemporal ecological succession of oral bacterial and fungal microbiomes and to elucidate the role of cross-kingdom microbial interactions during the natural progression of S-ECC.Design A 27-month longitudinal study followed 24 initially caries-free children who ultimately developed cavitated lesions. Samples were collected across four distinct spatial niches: Saliva (S), supragingival plaque from healthy tooth surfaces (HM), plaque from carious tooth surfaces (DM), and carious lesion tissue (CL). Dynamics were evaluated using bacterial full-length 16S rRNA (V1-V9) and fungal ITS2 sequencing, coupled with ecological and co-occurrence network analyses.Results Bacterial and fungal communities exhibited divergent successional trajectories. Bacterial community structure was predominantly shaped by spatial niches, whereas fungal communities clustered primarily by time, indicating opportunistic characteristics. Crucially, cross-kingdom network analysis revealed a fundamental shift in microbial interaction patterns from antagonism in health to synergy in disease. As caries progressed, carious lesions exhibited near-exclusive positive bacterial‒fungal correlations, dominated by Streptococcus and Candida.Conclusions This study revealed that a cross-kingdom ecological shift‒from competition to cooperation‒drives caries pathogenesis, revealing novel microbial synergy as a key determinant of S-ECC and suggesting targeted interkingdom interventions.