The oral microbiome as a regulatory hub for systemic health: a systematic review of mechanistic links and clinical implications.

Background: The human oral microbiome is a highly diverse ecosystem with important roles in oral and systemic health. Beyond dental caries and periodontitis, oral dysbiosis has been increasingly implicated in the development of multiple non-communicable diseases. Objective: To systematically synthesize evidence on the mechanisms linking oral dysbiosis to systemic diseases and to summarize its diagnostic and therapeutic implications. Design: A systematic review was performed using major electronic databases. We screened 1,128 records and included 104 studies that met predefined eligibility criteria. Results: Evidence indicates that oral dysbiosis may influence systemic health through several mechanisms, including hematogenous dissemination of oral pathogens and virulence factors (e.g. lipopolysaccharide), chronic systemic inflammation, molecular mimicry in autoimmune disorders, and microbial metabolic byproducts. The reviewed studies support associations between oral microbiome alterations and atherosclerotic cardiovascular disease, type 2 diabetes, Alzheimer's disease, rheumatoid arthritis, and gastrointestinal cancers. The literature also highlights the promise of non-invasive oral microbiome-based biomarkers for early detection and disease monitoring. Emerging microbiome-modulating interventions, including probiotics, prebiotics, and bacteriophage therapy, show potential for restoring oral eubiosis and improving systemic outcomes. Conclusions: Oral dysbiosis is an important regulator of systemic disease processes and a promising target for diagnosis, prevention, and therapy. Integrating oral health and oral microbiome assessment into broader disease management may improve outcomes, although methodological standardization and stronger causal evidence are still needed.