Paraquat, a widely used
herbicide, causes environmental pollution, and liver injury in humans and animals. As a natural compound in fruits,
ellagic acid (EA) shows anti-inflammatory and
antioxidant effects. This study examines the beneficial effects of dietary EA against the
paraquat-induced hepatic injury and further explores the underlying molecular mechanisms using a piglet model. Post-weaning piglets are fed basal diet supplemented with 50 mg/kg, 100 mg/kg, or 200 mg/kg EA for 3 weeks. At week 2, hepatic injury is induced by 4 mg/kg
paraquat followed by 7 days recovery. EA supplementation significantly mitigates
paraquat-induced hepatic
fibrosis, steatosis, and high apoptotic rate. In agreement, EA supplementation reduces serum pro-inflammatory levels, ameliorates inflammatory cells infiltration into hepatic tissue, which are associated with suppressed NF-κB signaling during
paraquat exposure. In addition, EA supplementation significantly improves activities of antioxidative
enzymes which were correlated with activated Nrf2/Keap 1 signaling during
paraquat exposure. Furthermore, EA supplementation restores cecal microbial community during
paraquat exposure. The protective effect of EA is strongly linked with increased relative abundance of Lactobacillus reuteri and Lactobacillus amylovorus. Taken together, EA supplementation effectively reduced the occurrence of hepatic oxidative damage and
inflammation induced by
paraquat through modulating cecal microbial communities, which provides a novel nutritional therapeutic strategy for hepatic injury.