Zinc-L-selenomethionine (Zn-L-SeMet), a novel organic selenium (Se) source, shows great potential in alleviating oxidative stress. This study first evaluated the potential of Zn-L-SeMet to improve the health of weaned piglets and investigated underlying molecular mechanisms. In vivo, 240 weaned piglets were assigned to five dietary groups, namely, a control group (basal diet without Se) and four groups supplemented with Zn-L-SeMet (0.1, 0.2, 0.3, or 0.4 mg Se/kg in basal diet) for 42 days. In vitro, an oxidative stress model was established using hydrogen peroxide (H₂O₂) in porcine intestinal epithelial cells (IPEC-J2) to investigate the mechanisms of Zn-L-SeMet against oxidative damage. The results showed that Zn-L-SeMet improved growth performance, enhanced antioxidant and immune function, stimulated thyroid hormone secretion, and upregulated expression of selenoprotein genes. In vitro, Zn-L-SeMet reduced H₂O₂-induced apoptosis, promoted IPEC-J2 viability, and enhanced activities of antioxidant enzymes, while reducing lactate dehydrogenase release, malondialdehyde and reactive oxygen species levels. Furthermore, Zn-L-SeMet significantly increased the expression levels of Keap1, NQO1, HO-1, ARE, p-Nrf2, p-PI3K, and p-AKT, and protein ratio of p-Nrf2/Nrf2, PI3K/PI3K, and p-AKT/AKT compared to the H₂O₂ group (p < 0.05). In conclusion, Zn-L-SeMet improves health status with antioxidant potential in weaned piglets, and the mechanism is associated with activation of PI3K/AKT and Nrf2/Keap1 pathways.

Growth hormone has the potential to modulate inflammatory responses, alleviate intestinal injury, and preserve intestinal health. However, its limited availability from natural sources restricts further research and practical applications. Therefore, we optimized the coding sequence for porcine growth hormone (pGH) and constructed recombinant Lactococcus lactis (L. lactis) expressing pGH. The effect of L. lactis (pNZ8148-pGH) against intestinal damage was evaluated in mice with DSS-induced colitis. Orally administered L. lactis (pNZ8148-pGH) attenuated the symptoms of DSS-induced colitis, including weight loss, colon shortening, and elevated colonic damage scores (CDS), and improved colonic tissue morphology. Compared with the DSS group, L. lactis (pNZ8148-pGH) significantly reduced serum diamine oxidase (DAO) activity, colonic myeloperoxidase activity, and serum D-lactate and endotoxin levels while increasing colonic occludin and claudin-1 levels. Colonic tumor necrosis factor-α, interleukin-2 (IL-2), and interleukin-6 levels decreased significantly, whereas the interleukin-10 (IL-10) level increased after L. lactis (pNZ8148-pGH) administration. Furthermore, L. lactis (pNZ8148-pGH) significantly increased the numbers of colonic Ki67- and PCNA-positive cells and their positive indices. In addition, compared with the DSS group, L. lactis (pNZ8148) significantly decreased CDS, serum DAO activity, and colonic IL-2 level while increasing colonic occludin and IL-10 levels. In conclusion, oral administration of L. lactis (pNZ8148-pGH) maintained intestinal barrier integrity, suppressed inflammation, promoted mucosal repair, and alleviated DSS-induced colitis.