Exploring the Oral Resistome: From Metagenomics to Precision Oral Health.

Antimicrobial resistance (AMR) represents one of the foremost global public health threats, undermining the efficacy of antibiotic therapies across all clinical disciplines, including dentistry. The oral cavity, housing one of the most diverse microbial ecosystems in the human body, contains a largely underappreciated reservoir of antibiotic resistance genes (ARGs), collectively defined as the oral resistome. This review synthesises current evidence on the oral resistome across five thematic areas. First, we contextualise the global burden of AMR, highlighting its scale and implications for oral healthcare. Second, we define the oral resistome and characterise its composition, distribution across oral microhabitats, and the principal determinants that govern its structure and dynamics. Third, we critically appraise metagenomic approaches, from early culture-based and PCR-targeted methods to shotgun metagenomics and functional screening, that have expanded the resolution of resistome characterisation. Fourth, we examine multi-omics integration, including genomics, transcriptomics, and metabolomics, and its capacity to reveal the ecological and molecular drivers of resistance within the oral ecosystem. Finally, we explore how resistome profiling can inform precision oral health, enabling individualised antimicrobial stewardship, microbiome-based risk stratification, and patient-tailored preventive and therapeutic strategies in the era of personalised dentistry.