Long-term groundwater arsenic exposure is associated with altered arsenic methylation capacity and gut microbiota composition in a rural Chinese population

This study investigated the relationship between long-term groundwater arsenic exposure, arsenic methylation capacity, and gut microbiota in adults from rural northern China. Arsenic detoxification relies in part on methylation processes, and growing evidence suggests that the gut microbiome may participate in arsenic biotransformation, yet population-based data integrating exposure, metabolism, and microbial profiles remain scarce. We recruited 258 participants from two neighboring villages supplied by centralized wells with contrasting arsenic levels (control, n = 138; exposure, n = 120). Total urinary arsenic was measured in all participants, and arsenic species were quantified in a subgroup (n = 60) to derive primary and secondary methylation indices (PMI and SMI). Fecal metagenomes were sequenced to characterize taxonomic composition and functional potential based on KEGG and GO annotations. Individuals in the exposure village showed higher levels of urinary inorganic arsenic and methylated metabolites. While PMI was comparable between groups, SMI was significantly reduced among exposed individuals, indicating impaired secondary methylation. Arsenic exposure was also associated with pronounced alterations in gut microbial diversity and community structure. Several anaerobic taxa, largely linked to fermentative metabolism, were positively associated with SMI after multivariable adjustment. Functional analyses further revealed differences in pathways related to transport, environmental sensing, and metabolism. These findings suggest that chronic arsenic exposure is associated with reduced methylation efficiency and shifts in gut microbial composition and function, and that the gut microbiome may contribute to interindividual variability in arsenic metabolism and toxicity.