Taurine alleviated paraquat-induced oxidative stress and gut-liver axis damage in weaned piglets by regulating the Nrf2/Keap1 and TLR4/NF-κB signaling pathways

Abstract

Background: Oxidative stress can impair intestinal barrier function and cause liver damage, resulting in reduced animal productivity. Paraquat (PQ) induces significant oxidative stress in weaned piglets. The antioxidant, anti-inflammatory, and metabolic regulatory functions of taurine (Tau), a free amino acid that is widely distributed in the body, have been extensively studied. However, the mechanisms by which dietary Tau alleviates oxidative stress and gut-liver axis damage in weaned piglets remain unclear. Methods: Forty weaned piglets (20 males and 20 females; 6.41 ± 0.11 kg; 25 days old; Duroc × Landrace × Yorkshire) were used in a 2 × 2 factorial design to investigate the mechanism by which dietary Tau (0% or 0.4%) alleviates PQ-induced oxidative stress and gut-liver axis damage. We analyzed key biomarkers related to gut barrier function, mucosal damage repair, liver damage, gut-liver immunity, antioxidant capacity, systemic immune homeostasis, antioxidant levels, and gut microbiota diversity in piglets under normal and acute oxidative stress. In particular, we evaluated the coordinated regulation of gut-liver axis function mediated by Tau through the Nrf2/Keap1 (antioxidant) and TLR4/NF-κB (immune modulation) signaling pathways. Partial least squares path modeling and molecular docking were used to explore the intrinsic relationship between PQ, Tau, and the gut-liver axis. Results: PQ exposure impaired gut barrier function, increased the liver fibrosis area, and markedly affected gut microbial diversity (P < 0.05). Tau effectively alleviated PQ-induced oxidative stress by activating the Nrf2/Keap1 pathway and inhibiting the TLR4/NF-κB pathway. This enhanced gut barrier function, promoted mucosal repair, and significantly suppressed the concentration and circulation of lipopolysaccharides in the blood, consequently reducing liver damage (P < 0.05). This further facilitated the optimization of gut microbiota composition, thereby supporting the positive regulation of the gut-liver axis and improving systemic immune and antioxidant functions. Conclusions: Tau improved the health status of weaned piglets under both normal and stressed conditions by modulating the Nrf2/Keap1 and TLR4/NF-κB pathways, offering a potential new nutritional strategy for alleviating gut-liver damage.