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

Subchronic arsenic exposure caused histological damage to mouse intestinal tissue.

• HE staining revealed destruction of epithelial cells in arsenic-exposed mouse intestines.
• Arsenic exposure resulted in a reduction in the thickness of the muscularis propria.
• Increased infiltration of inflammatory cells was observed within the colonic tissue of arsenic-exposed mice.
• The mouse model used subchronic sodium arsenite (NaAsO2) exposure.

Arsenic exposure reduced intestinal barrier integrity as evidenced by decreased Occludin expression and elevated serum barrier damage biomarkers.

• Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein.
• Elevated concentrations of serum diamine oxidase (DAO) were observed, a biomarker indicative of intestinal barrier damage.
• Elevated concentrations of serum lactate (D-LA) were also observed as an additional biomarker of intestinal barrier damage.

Arsenic exposure altered gut microbiota composition at the family level without significantly affecting alpha or beta diversity.

• 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota.
• Arsenic exposure resulted in increased abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae.
• Muribaculaceae decreased following arsenic exposure.
• Changes in microbiota composition indicate intestinal microbiota dysbiosis despite unchanged diversity metrics.

Arsenic exposure increased pro-inflammatory cytokine levels while decreasing anti-inflammatory cytokine expression.

• Arsenic exposure led to increased protein levels of IL-1β, IL-6, and TNF-α.
• Arsenic exposure simultaneously decreased the expression of IL-10, an anti-inflammatory cytokine.
• These changes were observed in both the NaAsO2-exposed mouse model and the NaAsO2-treated NCM460 human colon mucosal epithelial cell line.

Arsenic activated the NF-κB signaling pathway, which was involved in colonic inflammation.

• Arsenic exposure activated the NF-κB signaling pathway in colonic tissue.
• The NF-κB pathway activation was associated with the observed intestinal inflammatory response.
• Both the mouse model and the NCM460 cell line model were used to investigate this mechanism.

Intervention with the NF-κB inhibitor PDTC significantly attenuated arsenic-induced intestinal inflammation.

• Pyrrolidine dithiocarbamate (PDTC) is a known inhibitor of the NF-κB signaling pathway.
• PDTC intervention significantly attenuated arsenic-induced intestinal inflammation.
• This finding supports the role of the NF-κB signaling pathway as a key mediator of arsenic-induced intestinal inflammation.