One of the most effective forms of therapeutic enteral nutrition is designated as "exclusive enteral nutrition" (EEN). EEN constitutes the monotonous enteral delivery of complete liquid nutrition and has been most explored in the treatment Crohn's disease (CD), a form of inflammatory bowel disease. While EEN's mechanisms of action are not clearly understood, it has been shown to modify the composition of the intestinal microbiome, an important component of CD pathogenesis. The current literature on the intestinal microbiome in healthy individuals and CD patients is reviewed with respect to EEN therapy. Further investigations in this field are needed to better understand the role and potential for EEN in chronic human disorders.