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

Abstract

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% <i>v</i>/<i>v</i> 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 (<i>SOD-1</i> and <i>SOD-2</i>) and the anti-inflammatory gene <i>IL-10</i> in the liver. Additionally, it caused apoptosis by dramatically altering the expression of genes associated with apoptosis including <i>Bax</i>, <i>Caspase-3</i>, and <i>Bcl-2</i>/<i>Bax</i>. Notably, AFB₁ exposure altered the gut microbiota composition, mainly manifested by <i>BF311</i> spp. and <i>Alistipes</i> 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.