An improved rat model for chronic inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) is an important cause of chronic disability in humans. Methods: We characterized a model of chronic IBD in young male Wistar rats by administering dextran sodium sulfate (DSS: 0%, 0.25%, 0.5%, or 1% in drinking water) for six weeks, with 0.5% DSS for twelve weeks, following DSS cessation or together with treatment with sulfasalazine for the last 6 weeks. We measured gastrointestinal characteristics including stool consistency, blood in stools, small intestine and colon length, intestinal transit and permeability, and gut microbiota, as well as extra-intestinal parameters including oral glucose tolerance, systolic blood pressure, fat and lean mass, and left ventricular stiffness. Results: At 6 weeks, 0.25-1% DSS produced gastrointestinal changes as diarrhea and blood in stools. At 12 weeks, 0.5% DSS produced chronic and sustained gastrointestinal changes, with marked infiltration of inflammatory cells throughout the gastrointestinal tract and crypt distortion. Firmicutes increased and Bacteroidetes and Actinobacteria decreased in DSS-treated rats. Changes were reversed by DSS cessation or sulfasalazine treatment. Gastrointestinal permeability and extra-intestinal parameters did not change, so DSS changes were limited to the gastrointestinal tract. Conclusion: Chronic 0.5% DSS produces selective and reversible gastrointestinal changes, providing an improved chronic model in rats that mimics human IBD for testing new interventions. (C) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.