The incidence of inflammatory bowel disease (IBD) is strikingly high in Western countries, implicating the role of Western diet in its etiology and pathogenesis. Western diet is characterized by high fat, low fiber, and high sugar. Despite clinical evidence of an association between high sugar diet and IBD susceptibility, the precise role of dietary simple sugars such as glucose, fructose, and sucrose in colitis pathogenesis is unknown. Using dextran sodium sulfate (DSS) and IL10-deficient mouse models of colitis, we studied the effect of simple sugars in colitis susceptibility.