Irritable bowel syndrome - An inflammatory disease involving mast cells

Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder - that is the presence of symptoms in the absence of demonstrable pathological abnormalities. In recent times, low grade inflammatory infiltrates in both the small and large bowel of some patients with IBS - often rich in mast cells, along with serological markers of low grade inflammation have focussed attention on IBS as an inflammatory disease. The observation that mast cells often lie in close association to enteric neurons, and in-vitro and in-vivo animal studies demonstrating that mast cell mediators may influence enteric motility provides a biologically plausible causal mechanism in IBS. Pilot studies on patients with IBS using the mast cell stabiliser sodium cromoglycate ('proof of concept') have been encouraging. The essential question remains why mast cells infiltrate the bowel of IBS patients. A disturbance of the 'brain-gut axis' is the current favoured hypothesis, whereby childhood stress or psychiatric comorbidity act via neuro-immune mechanisms to modulate low grade inflammation. An alternative hypothesis is that food allergy may be responsible. Serum specific IgE, and skin prick tests are not elevated in IBS patients, suggesting type 1 IgE mediated food allergy is not the cause. However questionnaire based studies indicate IBS patients have higher rates of atopic disease, and increased bronchial reactivity to methacholine has been demonstrated. In this review, we highlight the potential role of mast cells in IBS, and current and future research directions into this intriguing condition.