Ochratoxin A induces intestinal barrier impairment and concurrent hepatorenal toxicity in broiler chicks via modulation of autophagy, ferroptosis, and the intestinal microbiota.

Abstract

Ochratoxin A (OTA), a mycotoxin prevalent in contaminated feed, induces systemic toxicity upon intestinal absorption. In this study, broiler chicks were randomly divided into control, vehicle, or OTA-treated groups (0.05, 0.1, and 0.2 mg/kg bw/day). The results indicated that OTA caused histopathological damage to the intestine, liver, and kidney. Notably, OTA at 0.2 mg/kg bw induced hepatocellular injury, as evidenced by significantly elevated serum AST levels and hepatic inflammatory infiltration, and triggered renal damage characterized by increased relative kidney weight and tubular cell fragmentation. In the intestine, Structural alterations included shortened intestinal villi, deepened crypts, and disrupted tight junctions, accompanied by downregulated tight junction gene expression. Concurrently, OTA exposure induced intestinal oxidative stress. Mechanistically, OTA exposure reduced autophagy-related genes (SQSTM1, mTOR, and PI3K) while upregulating LC3B, ATG5, and BECN1, and triggered ferroptosis via increased jejunal mucosal iron accumulation, elevated ACSL4 and PTGS2 mRNA levels, and reduced GPX4, SLC7A11, and FTH1 expression. Additionally, 16S rRNA analysis revealed OTA changed the microbiota composition, marked by enrichment of g__norank_f__Muribaculaceae, g__Alloprevotella, g__Alistipes, and g__Bacteroides. Altogether, these findings indicated that OTA impaired the intestinal barrier resulting in intestinal injury, involving modulation of autophagy, ferroptosis, and microbial composition, while also inducing concurrent hepatorenal toxicity.