Dysbiosis of intestinal microbiota and hyperactive immune responses seem to be crucial for the uncontrolled inflammation in inflammatory bowel diseases (IBD). Modulation of the microbiome and immune stimulation of the intestinal epithelium were suggested as therapeutic approaches. In this study, live attenuated and dead bacterial cells of Salmonella Typhimurium SL7207 - a widely used bacterial vector for gene therapy were administered in DSS-induced colitis in mice. C57BL/6 mice were divided into four groups. The first group received pure water (CTRL). The other three groups received 2% dextran sulphate sodium (DSS) to induce colitis. Two DSS groups were treated with live attenuated (DSS live) or inactivated (DSS dead) Salmonella by gastric gavage. Intake of 2% DSS caused weight loss in all DSS groups compared to control mice with some improvement in DSS live group on the last day of the experiment. Significantly longer colon and improved stool consistency were reported in DSS live group, but not DSS dead group, when compared with DSS. Significant enlargement of spleens was observed only in DSS and DSS dead groups compared to control. Significant differences in stool consistency, colon length and spleen enlargement were observed between DSS live and DSS dead groups with beneficial effects of live bacteria. Interestingly, significant decrease in myeloperoxidase activity was detected in both, DSS live and DSS dead groups compared to the DSS group. On the basis of these results, progression of colitis seems to be beneficially influenced not only by live attenuated but to some extent also by inactivated Salmonella Typhimurium SL7207. Our results provide evidence that Salmonella-based gene therapy vectors are able to positively alter gut homeostasis during DSS-induced colitis.
Significance and impact of the study: Restoration of gut homeostasis has a great importance in IBD. Here, we tested the nonspecific effect of the strain Salmonella Typhimurium SL7207 on the course of colitis to find out whether the potential effect would be mediated by activity of live bacterial cells or by bacterial structures that are also present in dead bacteria. Live bacterial therapy of colitis showed a beneficial effect on clinical signs as well as on macroscopic and inflammatory markers of colitis. On the other hand, therapy with dead bacteria showed inconsistent effects, negative in most clinical outcomes, positive especially in myeloperoxidase activity. Our data indicate that the beneficial effect of bacterial gene therapy vectors carrying therapeutic genes might be, at least partially, caused by the bacterial vector instead of the therapeutic gene.
Keywords: Salmonella; bacterial vectors; colitis; dextran sulphate sodium; inflammatory bowel disease.
© 2016 The Society for Applied Microbiology.