Subchronic arsenic exposure induced intestinal flora dysbiosis and intestinal inflammation via activating the NF-κB signaling pathway

Arsenic (As) is a toxic metalloid commonly found in contaminated drinking water. It can be absorbed into the body through the intestinal tract and is metabolized and excreted via methylation and other processes. In this study, subchronic NaAsO ₂ exposure mice and NaAsO ₂ treated human colon mucosal epithelial cell line 460 (NCM460) models were used to study intestinal damage induced by arsenic. HE staining revealed that exposure to arsenic resulted in a significant decrease in the population of epithelial cells within the colonic tissue of mice. Additionally, the muscle layer exhibited thinning, indicating potential alterations in structural integrity. Furthermore, the results demonstrated a notable increase in the infiltration of inflammatory cells, suggesting an inflammatory response triggered by arsenic exposure in the colon. In mice exposed to arsenic, the levels of serum DAO and D-LA, which are indicators of intestinal damage, were elevated, while the protein Occludin, associated with the intestinal mucosa, was reduced. Furthermore, exposure to arsenic resulted in elevated levels of protein expression for IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic exposure, although it did not significantly affect the alpha and beta diversity of the bacterial flora in mice, resulted in changes to the abundances of five specific bacterial species with increasing of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae and Helicobacteraceae , and decreasing of Muribaculaceae by 16S rRNA sequencing analysis. Furthermore, arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. In conclusion, arsenic exposure damages the intestinal mucosa and disrupts the homeostasis of the intestinal flora, and NF-κB signaling pathway mediated intestinal inflammation by arsenic.