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.