Composite microecological agents have received widespread attention due to their advantageous properties, including safety, multiple effects, and low cost. This study was conducted to evaluate the protective effects of selenium (Se) nanoparticle (SeNP)-enriched Lactococcus lactis NZ9000 (L. lactis NZ9000-SeNPs) against enterotoxigenic Escherichia coli (ETEC) K88-induced intestinal barrier damage in C57BL/6 mice. The oral administration of L. latis NZ9000-SeNPs significantly increased the villus height and the number of goblet cells in the ileum; reduced the levels of serum and ileal interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma); and increased the activities of thioredoxin reductase (TrxR) and glutathione peroxidase (GSH-Px) compared with the ETEC K88-infected group not treated with L. lactis NZ9000-SeNPs. In addition, L. lactis NZ9000-SeNPs significantly attenuated the reduction of the expression levels of occludin and claudin-1, dysbiosis of the gut microbiome, and activation of the Toll-like receptor (TLR)/nuclear factor kappa B (NF-kappa B)-mediated signaling pathway induced by ETEC K88. These findings suggested that L. lactis NZ9000-SeNPs may be a promising and safe Se supplement for food or feed additives. IMPORTANCE The beneficial effects of microecological agents have been widely proven. Se, which is a nutritionally essential trace element for humans and animals, is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant to anti-inflammatory effects. However, sodium selenite, a common addition form of Se in feed and food, has disadvantages such as strong toxicity and low bioavailability. We investigated the protective effects of L. lactis NZ9000-SeNPs against ETEC K88-induced intestinal barrier injury in C57BL/6 mice. Our results show that L. lactis NZ9000-SeNPs effectively alleviate ETEC K88-induced intestinal barrier dysfunction. This study highlights the importance of developing a promising and safe Se supplement for the substitution of sodium selenite applied in food, feed, and biomedicine.
