Manipulation of Visceral Sensitivity and Immune System in IBS

Irritable bowel syndrome (IBS) is a common condition. At least 20% of the population suffer from IBS. The symptoms of abdominal pain, diarrhoea, constipation, bloating and difficulty with bowel motions are often disabling. Many of those affected are young and report a poor quality of life (QOL) to a degree that is similar to gut inflammatory conditions like ulcerative colitis and Crohn's disease. Yet the impact of IBS on patients' lives is often underestimated. This is probably because unlike inflammatory bowel disease, in which the bowel is inflammed and bleeds, the bowel in IBS looks normal. Instead the problem is of abnormal functioning of the gut the cause of which is unknown. Currently therapy for IBS is limited and until recently therapy has focused on treating the symptoms to improve QOL primarily because the underlying mechanism of IBS is poorly understood. However as more processes are being implicated in IBS e.g. visceral hypersensitivity (excessive response to sensory stimuli within the gut), infection, immune activation, dysmotility and abnormal gut fermentation , the potential for new therapies looks promising. The evidence that gut bacteria play a role in inducing IBS symptoms is due to observations of an improvement of IBS symptoms with probiotic therapy (bacterial supplements) and antibiotic therapy. Patients with IBS are hypersensitive to colorectal distension compared with healthy controls. Studies carried out in our unit have shown that visceral pain thresholds in response to stress are lower in patients with IBS compared with healthy volunteers. This hypersensitivity is apparent in response to both a physical and chemical stimulus but the triggers to visceral hypersensitivity remain largely unknown. Animal models suggest roles for both host immune response and intestinal bacteria in the induction of visceral hypersensitivity. This proposal will focus on further exploration of the mechanisms underlying visceral hypersensitivity to direct future