Bacteriophage-mediated biofilm control: a novel targeted strategy for the management of dental caries.

Dental caries, a globally prevalent chronic infectious disease, is driven by microbial dysbiosis of dental biofilm, involving multiple caries-associated colonizers. Conventional broad-spectrum antimicrobials and fluoride-based formulations often disrupt the commensal oral microbiota, contributing to antimicrobial resistance and imbalance of the oral ecosystem. In contrast, bacteriophage (phage) therapy has emerged as a promising precision strategy for caries control due to its high specificity, minimal off-target effects, and biofilm-disrupting capacity. Our review systematically summarizes recent advances in phage-based interventions for caries prevention and treatment. It describes the diversity and distribution of the oral phageome and its role in regulating oral microbial homeostasis. The review further details phages targeting key cariogenic bacteria, including S. mutans (e.g., φAPCM01, SMHBZ8), Actinomyces spp. (e.g., Av-1), and related phage enzymes. Core anti-bacterial and anti-biofilm mechanisms of oral phage are elucidated, such as direct bacterial lysis mediated by endolysins and holins, and inhibition and disassembly of biofilms through multiple mechanisms. Strategies for applying phages in caries management are also discussed, encompassing phage cocktails, combination therapies with conventional antimicrobials, and development of advanced delivery systems. Finally, current challenges and future directions of phage therapy are addressed. Overall, this review provides a comprehensive theoretical foundation for developing targeted, oral microbiome-friendly phage-based strategies against dental caries.