Effect of Budesonide on Dextran Sulfate Sodium Colitis in Mice Under Microbiota Depletion

Budesonide is widely used as anti-inflammatory drug in inflammatory bowel disease (IBD). We have shown that in mice with colitis induced by dextran sulfate sodium (DSS), treatment with budesonide ameliorates colitis but enhances bacterial and LPS translocation, resulting in systemic deterioration, suggesting an impairment of mucosal barrier function. In order to evaluate the importance of translocation, C57BL6/J pseudogerm free (PGF) mice with antibiotic induced depletion of the microbiota were used. Mice received DSS in drinking water and budesonide by gavage (3 micrograms/day) for 6 days. Surprisingly, the budesonide group showed increased body weight loss, rectal bleeding and disease activity index compared to the vehicle group. Hemoglobin and red blood cell were also decreased. Tight junctions were altered by budesonide, showing a decrease in ZO-1 and occludin by RT-qPCR. In addition, cyclin D1 was reduced and DKK1 was increased, suggesting a deleterious effect of the glucocorticoid on epithelial dynamics and restitution. Because the latter are modulated by the microbiota, we conclude that epithelial compliance is decreased by the absence of bacteria and this negative effect is enhanced by budesonide.