Adherent and invasive Escherichia coli (AIEC) appear to expand during inflammation and are observed in the ileal mucosa in subsets of Crohn’s patients. However, AIEC pathogenesis is poorly understood and cause-effect relationships between AIEC and IBD remain to be established. Importantly, a systematic comparison to determine whether in vitro phenotypes frequently used to define AIECs correlate with and predict a strain’s ability to contribute to disease in vivo has yet to be performed.