Protective effect of Lacticaseibacillus paracasei Jlus66 against Salmonella in a mouse model

Abstract Given the increasing prevalence of antibiotic-resistant strains and the presence of antibiotic residues in poultry products, the adoption of biocontrol strategies as alternatives to antibiotics has become increasingly crucial for ensuring food safety. This study aimed to evaluate the feasibility of using Lacticaseibacillus paracasei Jlus66 as a sustainable method to combat Salmonella Typhimurium ( S. Tm) and to investigate the underlying mechanisms. In vitro, Jlus66 inhibited the swimming motility of S. Tm by targeting its flagella, which significantly decreased its ability to cross the mucus layer, thereby minimizing damage to epithelial cells. In vivo, Jlus66 pretreatment effectively mitigated S. Tm invasion through multiple coordinated actions, including the enhancement of intestinal barrier function by up-regulating tight junction proteins (occludin, zonula occludens-1, and E-cadherin), modulating inflammatory responses by decreasing levels of interleukin-17, interferon and tumor necrosis factor-alpha while increasing interleukin-22, reshaping gut microbiota composition, and maintaining normal intestinal permeability. These combined effects resulted in a significantly reduced mortality rate and lowered S. Tm burden in the liver, spleen, colon, and cecum. These results illustrated that Jlus66 has protective properties by limiting the motility of S. Tm, reinforcing intestinal barrier integrity, modulating inflammatory responses, and restoring microbial homeostasis, thereby highlighting the potential of Jlus66 as a sustainable, antibiotic-alternative to improve food safety across the production chain.