Aflatoxin B1 Exposure in Sheep: Insights into Hepatotoxicity Based on Oxidative Stress,Inflammatory Injury,Apoptosis, and Gut Microbiota Analysis

The widespread fungal toxin Aflatoxin B₁ (AFB₁) is an inevitable pollutant affecting the health of humans, poultry, and livestock. Although studies indicate that AFB₁ is hepatotoxic, there are few studies on AFB₁-induced hepatotoxicity in sheep. Thus, this study examined how AFB₁ affected sheep liver function 24 h after the animals received 1 mg/kg bw of AFB₁ orally (dissolved in 20 mL, 4% v/v ethanol). The acute AFB₁ poisoning caused histopathological injuries to the liver and increased total bilirubin (TBIL) and alkaline phosphatase (AKP) levels. AFB₁ 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, AFB₁ exposure altered the gut microbiota composition, mainly manifested by BF311 spp. and Alistipes spp. abundance, which are associated with liver injury. In conclusion, AFB₁ can cause liver injury and liver dysfunction in sheep via oxidative stress, inflammation, apoptosis, and gut-microbiota disturbance.