Effects of Salmonella Outer Membrane Vesicles on Intestinal Microbiota and Intestinal Barrier Function.

Abstract

Salmonella enterica is one of the most important zoonotic pathogens causing foodborne gastroenteritis worldwide. Outer membrane vesicles (OMVs) are lipid-bilayer vesicles produced by Gram-negative bacteria, which contain biologically active components. We hypothesized that OMVs are an important weapon of S. enterica to initiate enteric diseases pathologies. In this study, the effects of S. enterica OMVs (SeOMVs) on intestinal microbiota and intestinal barrier function were investigated. In vitro fecal culture experiments showed that alpha diversity indexes and microbiota composition were altered by SeOMV supplementation. SeOMV supplementation showed an increase of pH, a decrease of OD630 and total short chain fatty acid (SCFA) concentrations. In vitro IPEC-J2 cells culture experiments showed that SeOMV supplementation did not affect the IPEC-J2 cell viability and the indicated genes expression. In vivo experiments in mice showed that SeOMVs had adverse effects on average daily gain (p < 0.05) and feed:gain ratio (p < 0.05), and had a tendency to decrease the final body weight (p = 0.073) in mice. SeOMV administration decreased serum interleukin-10 level (p < 0.05), decreased the relative abundance of bacteria belonging to the genera BacC-u-018 and Akkermansia (p < 0.05). Furthermore, SeOMV administration damaged the ileum mucosa (p < 0.05). These findings suggest that SeOMVs play an important role in the activation of intestinal inflammatory response induced by S. enterica, and downregulation of SCFA-producing bacteria is a possible mechanism.