Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic, and microbial factors involved in the development of the disease. A remarkable feature of this disease, especially, but not limited to childhood, is the effective response to exclusive enteral nutrition therapy and the observed benefit from exclusion of normal diet (principle of exclusivity). We reviewed the possible mechanisms of action of enteral nutrition for induction of remission and provided a hypothetical model (herein termed bacterial penetration cycle) that integrates dietary components, bacteria, susceptibility genes, and the innate immune response in the pathogenesis of Crohn's disease.