The microbiota, epithelial cells, and mucosal immune cells in the intestine comprise an important gastrointestinal coalition. The intestinal microbiota can exert both beneficial as well as deleterious effects on their animal hosts. They interact with the innate defenses provided by epithelial cells through microbial recognition receptors. This communication, under normal conditions, results in a state of controlled inflammation. This article will focus on several animal models of intestinal inflammation, in which spontaneous or induced mutations or other genetic manipulations result in severe alterations in one of the members of the gastrointestinal coalition. These animal models of colitis have shown that alterations in communication between members of this coalition ultimately lead to gastrointestinal disease.