An improved rat model for chronic inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD) is an important cause of chronic disability in humans. 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. 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. 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.