Sialyllactose Attenuates Inflammation and Injury of Intestinal Epithelial Cells upon Enterotoxigenic Escherichia coli Infection

Sialyllactose (SL), a bioactive trisaccharide abundant in porcine colostrum, demonstrates multifunctional properties including antimicrobial activity, immune regulation, and apoptosis inhibition. This research uncovers the mechanisms by which SL mitigates enterotoxigenic <i>Escherichia coli</i> (ETEC)-mediated damage to intestinal barrier integrity, employing IPEC-J2 porcine epithelial models. SL pre-treatment effectively blocked pathogen adhesion by competitively binding to cellular receptors, concurrently mitigating inflammation through significant suppression of <i>TNF-α</i>, <i>IL-1β</i>, and <i>IL-6</i> expression (<i>p</i> < 0.05). Notably, SL exhibited functional parallels to the NF-κB inhibitor BAY11-7082, jointly enhancing tight junction integrity via ZO-1 protein stabilization and inhibiting pro-inflammatory signaling through coordinated suppression of IκB-α/NF-κB phosphorylation cascades. The dual-action mechanism combines molecular interception of microbial attachment with intracellular modulation of the TLR4/MyD88/NF-κB pathway, effectively resolving both pathogenic colonization and inflammatory amplification. These findings position SL as a potential therapeutic application nutraceutical for livestock, with the capacity to address post-weaning porcine enteritis through functional feed formulations that synergistically enhance intestinal barrier resilience while curbing ETEC-mediated inflammatory pathogenesis.