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.

This study investigates the effects of long-term heavy metal exposure on the oral mucosal microbiota in women. By measuring both external environmental heavy metal exposure and internal heavy metal exposure indicators in the human body, it aims to elucidate the complex interactions between external environmental exposure and internal exposure, as well as their potential association with menopausal status. We analyzed oral microbial composition, function, and co-occurrence networks in 47 women from polluted and control areas. Heavy metal exposure significantly altered oral microbial diversity and functional pathways, with molybdenum (Mo) exhibiting a uniquely strong influence. Key metabolic pathways related to cardiovascular disease and carbohydrate metabolism were enriched in specific groups. Network analysis revealed a loss of keystone species and structural simplification in postmenopausal women from the polluted area. These findings suggest that heavy metal exposure alters oral microbial communities, and these alterations correlate with shifts in host metabolic pathways that are known to be associated with menopausal hormonal changes, potentially impacting women’s health during this transition. IMPORTANCE: This study reveals, for the first time, how chronic heavy metal exposure and menopause interact to disrupt the female oral microbiome. We identify Mo as a key metal, correlating strongly with specific bacteria and linked to downregulated cardiovascular and metabolic pathways. Critically, postmenopausal women in polluted areas exhibit a severe loss of keystone species and a collapsed microbial network structure. These findings position the dysregulated oral microbiome as a potential mechanistic link between environmental metal exposure and the heightened systemic risks—such as metabolic disorders and chronic inflammation—observed in postmenopausal women, highlighting new targets for preventive health strategies.