Characterising IBS subtypes and their response to Stress using MRI

Irritable Bowel Syndrome (IBS) is an extremely common condition which causes recurrent abdominal pain and erratic bowel habits. Although not fatal it can markedly reduce the sufferer‘s quality of life. IBS sufferers report a confusing range of disturbances of bowel habit including both diarrhoea and constipation, sometimes in the same patient. Patients reported symptoms are subjective and their significance is uncertain without a reliable way of measuring bowel function. More than half the IBS patients are abnormally anxious and two thirds believe their symptoms are stress related, which may explain the day to day variability in bowel habit. However it is difficult to objectively determine the effect of stress in any individual patient. We have recently developed and validated a new, non-invasive, Magnetic Resonance Imaging (MRI) technique to image small bowel and colon function. We believe that this could be a convenient test, costing less than many currently used tests, to objectively assess IBS patients and quantify their responsiveness to stress. We believe that stress acts on the gastrointestinal system by releasing a chemical, called CRF which acts via the nervous system and special cells in the gut called mast cells. This stimulates contractions and accelerate movements through the bowel. We have recently shown that MRI can detect the effect of CRF on the small bowel whose water content is reduced by 1/3rd within 30 minutes of injection. Previous studies show that CRF also stimulates colonic contractions. We aim to develop new methods of economically and effectively analysing colon images to compliment our method of studying small bowel water content and rates of movement through the gut. We will characterise the small and colonic water content and transit rates in various subtypes of IBS patients in whom we will also assess mast cells in the colonic mucosa. We will then test our hypothesis that the bowel and its mast cells in IBS patients are more sensitive to the stress by examining the correlation between MRI parameters, mast cell activation and psychological markers of stress. Our studies will lead to a better understanding of abnormalities of gut function and the effect of stress in IBS patients. They may also provide novel ways of predicting the response of individuals to different treatments.

Irritable Bowel Syndrome (IBS), characterised by recurrent abdominal pain and erratic bowel habits, is the commonest cause of outpatient consultation in gastroenterology. Over 50% of IBS patients are clinically anxious, 65% believe their typically erratic symptoms are linked to stress and many relate disease onset to a stressful event. However there are a number of key problems in the management of IBS. First IBS patients are heterogeneous, with different responses to therapy and most likely different aetiologies . Secondly there is no objective biomarker for IBS or its subtypes. We intend to develop objective MRI tests for IBS to address both these problems. Animal studies have shown that stress acting through Corticotrophin releasing factor (CRF) stimulates increased small intestinal and colonic motility via activation of mast cells, whose numbers are known to be increased in IBS. We have used novel magnetic resonance imaging (MRI) techniques to show that IBS patients with diarrhoea (IBS-D) have constricted small bowels with rapid transit. We have also shown that CRF reduces small bowel water content in healthy subjects by 36% and previous small studies have shown exaggerated stimulation of motility of small and large bowel segments by CRF in IBS.
We have previously found the constriction of the small bowel in IBS-D was correlated with anxiety which is equally common in all subtypes of IBS including those with constipation or mixed bowel habit. We hypothesise that stress will cause these subtypes to also have reduced small bowel water content and that the different bowel habit will depend on differences in colonic responsiveness which we will assess using our novel MRI parameters. We will optimize our imaging techniques to develop an efficient economical protocol to allow us to non-invasively define abnormalities of small bowel and colonic water content and transit in patients with various subtypes of IBS. Simultaneously we will assess mast cell numbers and their release of mediators in biopsies from the IBS patient‘s colonic mucosa. We will also assess psychological stress using psychometric questionnaires to test the hypothesis that the MRI assessments of the small and large bowel in IBS will show a link with stress. Our studies will provide a better understanding of the effect of stress on the intestine in IBS and provide a potential biomarker for characterizing individual patients and predicting their response to treatments