The Oral Virome in Dental Caries: From Ecological Disruptors to Therapeutic Opportunities.

Dental caries results from ecological dysbiosis of oral biofilms driven by frequent sugar exposure, yet the role of viruses, particularly bacteriophages, in this process remains underexplored. This review synthesizes current evidence on how the oral virome contributes to caries pathogenesis and examines emerging phage-based therapeutic strategies. The oral cavity harbors diverse viral communities, including eukaryotic viruses (herpesviruses, papillomaviruses) and prokaryotic viruses (bacteriophages). While herpesviruses like EBV, CMV, and HSV-1 do not directly demineralize teeth, they may act as ecological stressors by modulating host immunity, altering gingival crevicular fluid composition, and promoting inflammation that favors cariogenic bacterial activity. Bacteriophages function as key ecological regulators through "kill-the-winner" dynamics, maintaining microbial diversity by preying on dominant species. However, temperate phages can horizontally transfer genes encoding acidogenicity, biofilm formation, or antibiotic resistance, potentially accelerating dysbiosis. Metagenomic studies reveal distinct salivary phage signatures associated with caries, suggesting diagnostic potential. Preclinical evidence demonstrates that lytic phages targeting Streptococcus mutans (e.g., SMHBZ8, ΦAPCM01) disrupt biofilms in vitro and prevent caries in ex vivo and murine models. Phage-derived enzymes (endolysins, depolymerases) and peptides offer additional precision antimicrobials with minimal commensal disruption. Despite promising advances, significant translational gaps remain, including limited well-characterized phages, insufficient polymicrobial model testing, and absence of human clinical trials. Integrating virome ecology into caries management represents a paradigm shift from pathogencentric approaches toward ecosystem-based therapeutics, with phages offering targeted, self-replicating, and evolutionarily dynamic tools for restoring oral health.