Effects of Long-Term Heavy Metal Exposure on Oral Microbial Antibiotic Resistance Genes of Residents in the Mining and Smelting Area

Growing evidence highlights the role of heavy metals in driving the co-selection of an-tibiotic resistance genes (ARGs), and the human oral cavity is an important reservoir of ARGs. This cross-sectional study investigated the effects of heavy metal exposure on human oral microbiota and ARGs, collecting buccal mucosal and blood samples from residents in a heavy metal-contaminated area (Baiyin City) and a non-contaminated area (Yuzhong County, Lanzhou City). The results showed heavy metal exposure is associated with altered alpha and beta diversity of bacteria and ARGs in human oral cavities, with bacterial compositional shifts being the main factor in ARG variation. Metagenomic analysis revealed heavy metal exposure is linked to modifying the interactions in the bacterial community and between ARGs and metal resistance genes (MRGs), shown by simplified topological structures in bacterial and resistome networks, along with enhanced positive correlations among nodes. Neisseria, Haemophilus, Morococcus, Streptococcus, Staphylococcus, and Mycobacteroides as potential hosts for resistance genes in human oral cavity. Furthermore, blood metal quantification revealed distinct associations with resistance patterns. This study demonstrates significant associations between environmental heavy metal exposure and the oral resistome and emphasizes the role of bacterial community composition.