Aflatoxin B(1) Exposure in Sheep: Insights into Hepatotoxicity Based on Oxidative Stress, Inflammatory Injury, Apoptosis, and Gut Microbiota Analysis

The widespread fungal toxin Aflatoxin B(1) (AFB(1)) is an inevitable pollutant affecting the health of humans, poultry, and livestock. Although studies indicate that AFB(1) is hepatotoxic, there are few studies on AFB(1)-induced hepatotoxicity in sheep. Thus, this study examined how AFB(1) affected sheep liver function 24 h after the animals received 1 mg/kg bw of AFB(1) orally (dissolved in 20 mL, 4% v/v ethanol). The acute AFB(1) poisoning caused histopathological injuries to the liver and increased total bilirubin (TBIL) and alkaline phosphatase (AKP) levels. AFB(1) also markedly elevated the levels of the pro-inflammatory cytokines TNF-α and IL-6 while considerably reducing the expression of antioxidation-related genes (SOD-1 and SOD-2) and the anti-inflammatory gene IL-10 in the liver. Additionally, it caused apoptosis by dramatically altering the expression of genes associated with apoptosis including Bax, Caspase-3, and Bcl-2/Bax. Notably, AFB(1) exposure altered the gut microbiota composition, mainly manifested by BF311 spp. and Alistipes spp. abundance, which are associated with liver injury. In conclusion, AFB(1) can cause liver injury and liver dysfunction in sheep via oxidative stress, inflammation, apoptosis, and gut-microbiota disturbance.