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

Arsenic is a prevalent environmental contaminant found in contaminated drinking water. However, the effects of arsenic exposure on the intestinal tract and the specific mechanisms of action remain unclear. In this study, we utilized subchronic sodium arsenite (NaAsO2)-exposed mice and the NaAsO2-treated human colon mucosal epithelial cell line 460 (NCM460) models to investigate the intestinal damage induced by arsenic. Hematoxylin-eosin (HE) staining revealed that the intestines of mice exposed to arsenic exhibited histological damage, characterized by the destruction of epithelial cells, a reduction in the thickness of the muscularis propria, and an increased infiltration of inflammatory cells within the colonic tissue. Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein, accompanied by elevated concentrations of two biomarkers indicative of intestinal barrier damage: serum diamine oxidase (DAO) and lactate (D-LA). Analysis using 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota. However, it resulted in changes in the abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae increased, while Muribaculaceae decreased. Furthermore, exposure to arsenic led to increased protein levels of IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. Finally, intervention with Pyrrolidine dithiocarbamate (PDTC) significantly attenuated arsenic-induced intestinal inflammation. In conclusion, arsenic exposure compromises the integrity of the intestinal mucosa and disrupts the homeostasis of the intestinal microbiota. Additionally, arsenic mediates intestinal inflammation through the NF-κB signaling pathway.