An antagonist of the interaction between the Gp96 receptor and E. coli AIEC strains, for the prevention or treatment of inflammatory bowel disease. The antagonist is for specifically blocking or reducing the interaction between Gp96 receptor and the outer membrane vesicles (OMVs), typically the outer protein membrane OmpA of E. coli AIEC strains. The inventions provides for pharmaceutical compositions containing such an antagonist, which may be an antibody against gp96 or OmpA, or a gp96 or OmpA polypeptide. It may be combined to an antagonist of the interaction between the CEACAM6 receptor and E. coli AIEC strains, such as an anti-CEACAM6 antibody, a CEACAM6 polypeptide, or a mannoside or particle having a mannose unit. The invention also relates to a method for the diagnosis of inflammatory bowel disease, or of the determination of a predisposition of a person to develop inflammatory bowel disease.