Involvement of intestinal microbes in the pathogenesis of chronic inflammatory bowel diseases (IBD, including Crohn disease and ulcerative colitis) is well established. However, the mechanisms by which bacteria lead to intestinal injury in IBD remain unclear and are the focus of current research. Using adherent-invasive Escherichia coli (AIEC) strain LF82, which is linked to Crohn disease, we recently demonstrated the ability of these intestinal microbes to disrupt the integrity of epithelial cells in an in vitro cell model. This disruption provides the bacteria a capacity to penetrate into and beyond the epithelial monolayer, replicate in cells, disseminate within the host, and induce a chronic immune response. These findings provide a link between microbes related to IBD, disruption of the intestinal epithelial cell barrier, and disease pathogenesis.In this addendum, we provide a synopsis on current data concerning the role of AIEC in the pathogenesis of intestinal inflammation, summarise our recent findings, and highlight the central role of the epithelium in mucosal defence. We also discuss, in more detail, the potential implications of our findings and present ideas for future studies and targets for intervention.