The treatment of active mucosal inflammation in ulcerative colitis remains challenging. Current therapies have limited efficacy and may be associated with clinically significant adverse effects. There is room for new therapeutic approaches. While nearly all of our current pharmacological approaches involve attacking various immune and inflammatory pathways in order to facilitate healing, few in the clinician’s current arsenal are directed towards enhancing or protecting the colonic epithelial barrier. Is this situation about to change?

The understanding of the pathogenesis of ulcerative colitis has not considerably progressed over the last decade. The proponents of concepts that the primary abnormalities lie within immune and inflammatory mechanisms have stumbled in attempts to explain the striking features of ulcerative colitis, such as the diffuse nature of the inflammation, its confinement to the mucosal compartment, and its distribution in the large bowel. The alternative concept that primary abnormalities lie within an abnormal epithelial barrier sits more comfortably with these characteristic features of the disease.¹ The barrier has regional differences in structure, composition, and function, which offer simple explanations for, for example, disease distribution. The nature of the inflammatory response in ulcerative colitis—intense polymorph infiltration and predominant antibody mediated (T_H2) responses with less prominent T cell activation—is most consistent with exposure of the immune system to large numbers of different “foreign” molecules.² Such events might be anticipated in a situation where multiple molecules are able to pass through a deficient epithelial barrier. This is in marked contrast with the situation in Crohn’s …