Host-microbiome-immune disequilibrium in oral disease: mechanisms, dysbiosis, and precision therapeutics

Background: The oral cavity harbors a dynamic microbial ecosystem that interacts with epithelial barriers, host immunity, and local tissue environments. Disruption of this balance is increasingly recognized as a key driver of major oral diseases, including periodontitis, dental caries, and oral squamous cell carcinoma (OSCC). However, the biological links between microbial ecology, immune regulation, and disease progression are insufficiently integrated, limiting mechanistic understanding and translational progress. Methods: This structured narrative review searched PubMed/MEDLINE, Web of Science, Embase, and Scopus for relevant studies on oral microbiome ecology, mucosal immunity, dysbiosis, oral diseases, and emerging therapies. Evidence was narratively synthesized across microbiome ecology, mucosal immunology, disease pathogenesis, and translational research, with consideration of study type, mechanistic relevance, and translational significance. Results: Current evidence supports that oral homeostasis relies on coordinated interactions among commensal microbial communities (CMC), epithelial and salivary barriers, and immune surveillance. Dysbiosis disrupts this equilibrium by promoting the expansion of pathobionts, amplifying inflammatory responses, and contributing to tissue injury. This systems-level perspective helps explain the persistence and heterogeneity of oral diseases beyond pathogen-centered models. Emerging technologies are reshaping this field. These include microbiome-modulating therapies, host-directed interventions, multi-omics approaches, and artificial intelligence (AI). These approaches are advancing disease stratification, biomarker discovery, and precision therapeutic development. Conclusion: Oral diseases should be understood as disorders of host-microbiome-immune disequilibrium rather than as isolated infections. This perspective highlights the need for integrated strategies that consider microbial ecology, immune regulation, epithelial barrier function, and clinical context to improve prevention, diagnosis, and treatment in precision oral medicine.