Oral Phageome as Potential Modulators of Periodontal Dysbiosis. A Systematic Review

INTRODUCTION: The oral phageome, comprising bacteriophages inhabiting the oral cavity, has been proposed as a potential modulator of periodontal health and disease. This systematic review synthesizes current evidence on interactions between bacteriophages, key periodontal bacteria, and the host in periodontitis. METHODS: The review followed PRISMA guidelines and was registered in PROSPERO (CRD420250653631). A systematic search of the literature was conducted from January 2025 up to March 2025. Two independent PECOS strategies were applied to include clinical/observational and ex vivo studies. Risk of bias was assessed using the Newcastle-Ottawa Scale, Joanna Briggs Institute Checklist, and a modified SYRCLE's tool. RESULTS: Of 965 records identified, 17 studies, comprising 623 patients, met the inclusion criteria. Clinical studies suggest alterations in the oral phageome in periodontitis, with increased abundance and activity of lytic phages, whereas temperate phages appear more prevalent in periodontal health. Ex vivo studies demonstrate that bacteriophages can interact with major periodontopathogens, influencing bacterial virulence, biofilm behavior, and horizontal gene transfer. CONCLUSION: Current evidence does not establish a causal role for bacteriophages in periodontitis. Nevertheless, phages may function as contextual modulators of periodontal dysbiosis, particularly in A. actinomycetemcomitans-associated disease. Further longitudinal and functional multi-omics studies are needed to clarify their clinical relevance. TRAIL REGISTRATION: PROSPERO ID: CRD420250653631.