Prevotella denticola promotes caries by inducing oral microbial dysbiosis

While the role of oral microbial dysbiosis in cariogenicity is widely appreciated, it remains unclear whether some resident microorganisms are active contributors in this process. Recently, increasing evidence showed that Prevotella spp. are associated with caries whereas the identified roles at species level remain undefined. This study aimed to analyze the effects of Prevotella denticola on microbial ecosystems and pathogenic mechanisms associated with caries. Here, we applied metagenomics to supragingival microbiota (dental plaque) samples from 62 adults to identify disease-relevant species. P. denticola was highly enriched in caries-affected individuals (P < 0.001). The dynamic biofilm formation, spatial arrangement, and cariogenic activity of oral biofilms with or without P. denticola were examined via multiscale/computational imaging and virulence assays. P. denticola, exerting a previously unidentified mechanism in supragingival biofilms, promoted oral biofilm cariogenicity through altering the microbial ecosystem and biofilm structure. In vivo studies demonstrated that P. denticola induced the formation of a more cariogenic biofilm on supragingival tooth surfaces. Collectively, P. denticola has an ecological impact on the mixed oral microbiota and disrupts microbial equilibrium. These findings indicated that P. denticola infection plays a critical role in caries occurrence. 1. Prevotella denticola disrupts oral microbial homeostasis to exacerbate cariogenic biofilm formation. 2. Clinical metagenomics reveals P. denticola enrichment in caries lesions linked to dysbiosis markers. 3. In vitro/vivo models demonstrate P. denticola-driven acidogenicity and EPS augmentation in caries progression.