Translational potential of oral microbiome-based interventions for oral and systemic health

The oral microbiome is increasingly recognized as a mediator linking oral dysbiosis to cardiovascular, metabolic, inflammatory, and other extraoral diseases. Beyond etiologic associations, growing attention is now focused on whether the oral microbial ecosystem can be targeted therapeutically. This review summarizes the mechanistic basis of oral–systemic crosstalk and its implications for microbiome-based therapy. We focus on four emerging platforms: oral-resident next-generation probiotics (NGPs), engineered bacteria, cell-free microbial products, and oral microbiota transplantation (OMT). For cell-free approaches, we discuss postbiotics, postbiotic-like cell-free supernatants (CFSs), and vesicle-based products, including bacterial membrane vesicles (MVs) and outer membrane vesicles (OMVs), as related modalities with distinct compositions and translational considerations. We further compare their major translational barriers, including colonization durability, safety control, manufacturing standardization, and regulatory uncertainty. Oral microbiome-based interventions represent promising but early-stage adjunctive or risk-modifying strategies for systemic disease prevention and management. Mechanistic validation, platform optimization, and translational standardization remain essential for clinical application.