Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). The paper of Carvalho et al. recently reported that CD associated AIEC colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM6 acting as a receptor for type 1 pili produced by AIEC bacteria. AIEC also induce CEACAM6 expression by intestinal epithelial cells directly by adhering to host cells and indirectly via increased secretion of TNF-α from AIEC-infected macrophages. Patients expressing a basal level of CEACAM6 in ileum could be predisposed to develop ileal CD and blocking interaction between type 1 pili and CEACAM6 might serve as a specific means of disrupting the colonization and the subsequent inflammatory amplification loop.