Maternal supplementation of hydroxy-analogue of selenomethionine strengthens offspring intestinal tight junction by activating Wnt/β-catenin signal and inhibition of apoptosis in intestinal epithelial cells

The intestinal barrier is pivotal for systemic homeostasis, with its dysfunction implicated in numerous gastrointestinal pathologies. This study elucidates effects and mechanisms by which maternal hydroxy-analogue of selenomethionine (2-hydroxy-4-methylselenobutanoic acid, HMSeBA) supplementation augments intestinal defense in offspring. Employing complementary in vivo and in vitro approaches, sows received HMSeBA during gestation period, and jejunal tissues from neonatal/weaned offspring were analyzed. In vitro, IPEC-J2 intestinal epithelial cells were treated with HMSeBA to recapitulate maternally transferred effects, followed by H 2 O 2 challenge to induce oxidative stress. Maternal HMSeBA enhanced offspring intestinal barrier integrity, demonstrated by elevated expression of tight junction proteins (occludin, Zo-1), attenuated oxidative damage through enhanced glutathione peroxidase activity in weaned piglets (postnatal day 28) after LPS infection, and suppressed H 2 O 2 -triggered apoptosis in IPEC-J2 cells. Mechanistically, HMSeBA potentiated cellular antioxidant defenses via increase glutathione peroxidase activity, thereby inhibiting excessive apoptosis in intestinal cells, while concurrently facilitating β-catenin nuclear translocation and upregulating Wnt/β-catenin targets (TCF4, LEF1), thereby preserving epithelial barrier integrity. These findings identify HMSeBA as a novel maternal nutritional strategy that coordinates redox homeostasis and proliferative signaling to fortify intestinal resilience, providing a translational framework for preventing early-life enteropathies.