Autoimmunity and Irritable Bowel Syndrome: New Pathophysiology

Recent data suggest that symptoms in a subset of subjects with irritable bowel syndrome (IBS) result from an overabundance of bacteria in the small intestine that in turn results from an initial case of acute bacterial gastroenteritis. In fact, up to 10% of patients who have acute bacterial gastroenteritis develop postinfectious IBS (PI-IBS). Based on these findings, a new animal model of PI-IBS has been validated using a pathogen commonly associated with IBS in humans, Campylobacter jejuni. The development of this new model has allowed the discovery of novel mechanisms in the genesis of IBS. The first of these is that a toxin common to many types of bacterial pathogens, cytolethal distending toxin (Cdt, specifically the active subunit CdtB), is important in the development of IBS following acute gastroenteritis. However, the events are not mediated through direct toxicity of CdtB but rather via molecular mimicry and autoimmunity. This molecular mimicry results in the development of autoimmunity to human vinculin, a protein important to neuronal migration and cell adherence. The detection of these antibodies is now the basis for a newly developed diagnostic test for diarrhea-predominant IBS. In this paper, the steps that led to the discovery that a subset of IBS is an organic autoimmune disease are discussed.