Lactococcus lactis
(
L. lactis
) NZ9000, which has been genetically modified, is the most commonly used host strain for nisin regulated gene expression. Selenium (Se) is an essential trace element in the diet of humans and animals important for the maintenance of health and growth. Biosynthesized Se nanoparticles (SeNPs) that use microorganisms as a vehicle are uniquely advantages in terms of low costs, low toxicity and high bioavailability. This study was aimed at preparing novel functionalized SeNPs by
L. lactis
NZ9000 through eco-friendly and economic biotechnology methods. Moreover, its physicochemical characteristics, antioxidant and anti-inflammatory activities were investigated.
L. lactis
NZ9000 synthesized elemental red SeNPs when co-cultivated with sodium selenite under anaerobic conditions. Biosynthesized SeNPs by
L. lactis
NZ9000 were mainly capped with polysaccharides and significantly alleviated the increase of malondialdehyde (MDA) concentration, the decrease of glutathione peroxidase (GPx) and total superoxide dismutase (T-SOD) activity in porcine intestinal epithelial cells (IPEC-J2) challenged by hydrogen peroxide (H
2
O
2
). SeNPs also prevented the H
2
O
2
-caused reduction of transepithelial electrical resistance (TEER) and the increase of FITC-Dextran fluxes across IPEC-J2. Moreover, SeNPs attenuated the increase of reactive oxygen species (ROS), the reduction of adenosine triphosphate (ATP) and the mitochondrial membrane potential (MMP) and maintained intestinal epithelial permeability in IPEC-J2 cells exposed to H
2
O
2
. In addition, SeNPs pretreatment alleviated the cytotoxicity of Enterotoxigenic
Escherichia coli
(ETEC) K88 on IPEC-J2 cells and maintained the intestinal epithelial barrier integrity by up-regulating the expression of Occludin and Claudin-1 and modulating inflammatory cytokines. Biosynthesized SeNPs by
L. lactis
NZ9000 are a promising selenium supplement with antioxidant and anti-inflammatory activities.