The Effects of Change in the Intestinal Microbiota Through Antibiotics Administration on the Manifestion of DSS Colitis

Abstract

Background: The role of intestinal microbiota in maintaining mucosal homeostasis cannot be more emphasized. IL-17A have been shown to have both pathogenic and protective roles in animal models of colitis. We investigated the effects of intestinal microbiota change through antibiotics administration on dextran sodium sulfate (DSS) colitis in IL-17A-/- mice. Methods: C57BL/6 wild-type (WT) and IL-17A-/- mice were assigned to different three groups: control group without treatment, antibiotics (vancomycin, ampicillin, neomycin and metronidazole) plus subsequent 1.7% DSS treated group, and DSS treated group. Clinical activities including weight loss and histologic findings of colonic segments were examined. Proinflammatory cytokine levels were measured by ELISA in the supernatants of colonic tissue explants. To characterize the change of intestinal microbiota, high throughput Illumina MiSeq sequencing for sequential feces was performed. Results: Antibiotics treatment induced a transient weight loss in both WT and IL-17A-/- mice. WT mice developed more severe DSS colitis than IL-17A-/- mice. After antibiotics treatment, both mice displayed significantly enlarged ceca similar to germ-free mice. Antibiotics treatment attenuated DSS-induced increase of histologic inflammation and proinflammatory cytokine levels, especially in WT mice. There was a distinct difference in intestinal microbial composition between WT and IL-17A-/- mice. In both mice, after antibiotics treatment, the proportion of Firmicutes decreased while Proteobacteria increased in the phylum level, and Lachnospiraceae and Lactobacillaceae decreased while Enterobacteriaceae increased in the family level. Conclusions: IL-17A ablation decreases severity of colitis in DSS murine model. The change of intestinal microbiota through antibiotics administration affects the susceptibility of DSS colitis.