Abstract
BACKGROUND: The oral cavity is an important yet understudied reservoir of antimicrobial resistance genes (ARGs), potentially shaped by geographic variation in antibiotic usage. OBJECTIVE: To compare the oral resistomes of healthy adults from Thailand and Norway, two countries with contrasting antimicrobial use practices, using shotgun metagenomic sequencing. DESIGN: Stimulated saliva samples were collected from healthy adults in Thailand (n = 43) and Norway (n = 50). ARGs were identified with AMRPlusPlus against the MEGARes database, and microbial taxonomy was profiled with KrakenUniq. Diversity metrics, ordination, and clustering analyses assessed resistome and microbiome structures. RESULTS: Thai samples exhibited significantly greater ARG richness, evenness, and diversity (p < 0.001), driven by higher abundances of multi-biocide, nucleoside, and copper resistance genes. Norwegian samples were enriched in aminoglycoside, sulfonamide, and quaternary ammonium compound resistance genes. Both cohorts shared core oral genera, but Thai samples showed greater taxonomic richness without differences in overall microbiome diversity. Non-metric multidimensional scaling and PERMANOVA revealed stronger geographic separation for resistomes (R² = 0.639) than microbiomes (R² = 0.382). Co-occurrence networks highlighted structured associations between ARG groups and bacterial genera, suggesting ecological influences beyond taxonomic composition. CONCLUSIONS: These results reveal distinct geographic signatures in the oral resistome that are not fully explained by microbiome structure, reflecting the influence of local ecological and societal factors, including antimicrobial exposure. The findings highlight the oral cavity as a dynamic ARG reservoir and support its inclusion in regional antimicrobial resistance surveillance to inform public health strategies.