Besides its role in repelling enteropathogenic infections, the gastrointestinal tract is in intimate contact with commensal microbiota. Tremendous advances have been made in determining the pivotal role of the microbiota in both tissue homeostasis and metabolism, as well as in the initiation and maintenance of inflammatory lesions in inflammatory bowel diseases. A better understanding of human gut microbiota could provide innovative targets for treating and/or curing such common immunopathologies of the gastrointestinal tract.