The mucosal immune system faces the delicate task of co-existence with a luxuriant commensal intestinal bacterial flora (10¹² bacteria/g faeces in the colon, and roughly 10³ different species, with anaerobes predominating). Yet a protective immune response to invasive enteric pathogens is also mandatory. Of course, any commensal organism can become a pathogen in appropriate circumstances, and the magnitude of this balancing act is illustrated by the similarity between proteins of the harmless commensal Escherichia coli and its pathogenic derivatives (or the Shigellagenus). The essential differences between innocent and harmful bacteria reside in toxin production and qualities of adherence to, or penetration of, the intestinal epithelial cell layer.

The barrier function of the intestine is clearly disrupted in active inflammatory bowel disease (IBD), with evidence for greater systemic penetration by commensal organisms. Whether abnormal intestinal permeability precedes intestinal inflammation in individuals predisposed to IBD, is still unclear, although it is a major feature of Crohn’s disease relapse. The “passive” intestinal barrier (of the epithelial cell layer linked by junctional complexes and overlaid with mucus) is certainly not (in real life) as fixed as one might suppose.1 We constantly face insults to barrier function, either through our own actions (ingestion of non-steroidal anti-inflammatory drugs, alcohol) or from intestinal pathogens. Epithelial cells are also actively involved in defence through …