Postbiotics and phage synergy in precision oral microbiome engineering: systems biology strategies targeting...

Dental caries continues to represent a major global public health concern and arises from complex ecological shifts within oral biofilms. The dominance of Streptococcus mutans, in combination with broader microbial imbalance and interactions involving the oral virome, plays a central role in disease progression. Although established preventive measures such as fluoride therapy and mechanical plaque control reduce enamel demineralization and microbial load, they do not comprehensively address dysbiosis, virulence regulation, or host-microbial signaling dynamics. Postbiotics are non-viable microbial products or metabolic derivatives with biological activity, are gaining attention as targeted modulators of the oral ecosystem. These agents include organic acids, exopolysaccharides, bacteriocins, and structural components derived from inactivated probiotic cells. Through diverse mechanisms, postbiotics can reduce acidogenic potential, weaken extracellular matrix integrity within biofilms, disrupt bacterial communication systems, and modulate mucosal immune pathways. Such effects may limit colonization efficiency and pathogenic behavior of S. mutans while preserving commensal balance. Emerging strategies propose combining postbiotics with bacteriophage-based approaches, immunomodulatory platforms, and innovative delivery systems such as nanoformulations and bioadhesive matrices to improve site-specific efficacy. Advances in multi-omics technologies, systems biology modeling, and artificial intelligence-driven diagnostics further support the development of personalized interventions tailored to individual microbial signatures. In addition, postbiotic-mediated modulation of viral-bacterial interactions and horizontal gene exchange may contribute to restoring ecological stability and reducing antimicrobial resistance dissemination. This review integrates current knowledge on postbiotic-driven regulation of the oral microbiome and virome and examines their potential role in precision-oriented caries management. Addressing translational challenges, including formulation stability, safety evaluation, regulatory pathways, and comprehensive virome profiling, will be critical for future clinical application.