Co-exposure to deoxynivalenol and hexavalent chromium is associated with intestinal injury, dysbiosis, and activation of ferroptosis and pyroptosis related pathways in broilers.

Abstract

The combined pollution of deoxynivalenol (DON) and hexavalent chromium [Cr(VI)] during crop and food processing poses a serious threat to the intestinal health of poultry and humans. However, the specific regulatory mechanisms underlying intestinal toxicity induced by DON and Cr(VI) co-exposure in broilers remain unclear. This study assessed the toxic impacts of combined DON and Cr(VI) on small intestinal microbiota and barrier function in broilers. It also clarified the regulatory mechanisms and correlation analysis of intestinal ferroptosis and pyroptosis induced by combined toxins. The results showed that exposure to DON and/or Cr(VI) induced inflammatory cell infiltration and oxidative stress. Meanwhile, this mixed toxin caused an imbalance in the intestinal microbiota, and damaged the intestinal barrier. This resulted in elevated serum levels of DAO, LDH and D-LA, reduced the number of goblet cells, the expression of tight junction proteins, and triggered ferroptosis and pyroptosis. Transcriptome screening revealed that the differentially expressed genes (DEGs) were primarily enriched in the NF-κB, NOD-like receptor and ferroptosis signaling pathways. And this is closely associated with intestinal microbiota dysbiosis. Furthermore, DON and/or Cr(VI) poisoning can cause ileal iron overload, increase the serum levels of IL-18 and IL-1β. It inhibits Nrf2/HO-1/GPX4 and activate the TLR4/NF-κB/NLRP3 signaling pathway. In conclusion, this study confirmed that DON and/or Cr(VI) could induce intestinal microbiota dysbiosis, disrupt intestinal barrier function, trigger ferroptosis and pyroptosis. These two pathogenic mechanisms create an amplification effect, jointly exacerbating the damage to the small intestine of broilers.