Salmonella Typhimurium is a significant pathogen causing diarrhea in weaned piglets, capable of triggering systemic inflammation and severe intestinal damage. As bioactive components of gut microbiota, extracellular vesicles (EVs) derived from Lactobacillus johnsonii (Lj-EVs) are likely to penetrate the intestinal mucus layer and reach host cells, potentially mediating host-microbiome interactions. Here, we found that Lj-EVs improved the intestinal barrier and attenuated intestinal injury in mice infected with S. Typhimurium. Multi-omics analysis showed that Lj-EVs intervention enriched mucin-utilizing Akkermansia. Moreover, Lj-EVs were associated with metabolic alterations, characterized by enhanced oxidative phosphorylation during homeostasis and suppression of HIF-1α-mediated glycolysis during infection. Proteomic profiling showed that Lj-EVs enriched functional proteins related to oxidative phosphorylation, indicating their potential immunomodulatory role. Notably, Lj-EVs modulated macrophage-mediated immune responses, contributing to limiting bacterial dissemination and alleviating intestinal inflammation. In conclusion, our study demonstrates that Lj-EVs alleviate Salmonella infection by reducing bacterial burden and confer metabolic and immunomodulatory benefits. These findings provide new evidence for future investigation of the protective roles of probiotic vesicles.
Wu et al. (Wed,) studied this question.