Identifying deficient colonic bacterial fermentation in patients with ulcerative colitis in remission

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Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease (IBD) characterised by inflammation in the lining of the large bowel. Recent studies of the bacterial populations that normally reside in the large bowel (gut microbiota) have shown abnormalities (i.e., dysbiosis) in the faeces of patients with UC. Our research group has found evidence that the ability of the gut microbiota to ferment carbohydrates may be markedly defective and this cannot be corrected by simply providing more dietary fibre. Such fermentation is an important function of the microbiota as it delivers breakdown products that include short-chain fatty acids such as butyrate to the lining cells of the colon. Butyrate is the major source of nutrition for those cells and also has anti-inflammatory and anti-tumour-producing effects. This observation has potentially large implications for how we manage UC. If it is true, then manipulation of the bacteria and of the specific carbohydrate substrates they see by, for example, dietary manipulation of the types of carbohydrates they eat might have therapeutic benefit. Furthermore, such fermentation lowers acidity (pH) in the bowel and this lowering is utilised for the activation of some drugs commonly used in UC (e.g. mesalazine). Defective fermentation might lead to poor activation of those drugs and lack of effectiveness. The major problem with studying fermentation in the large bowel is that most occurs in the proximal part of the large bowel – i.e., the part furthest away from the anus - and we have only been able to study it indirectly. Using swallowed capsule technology that transmits information to a transmitter worn by the patient (as used by the ‘pill-camera’), a new wireless pH-motility device, has been developed. This device is able to capture measurements for transit (speed of passage through the gut) and pH in real time and in a non-invasive manner as it travels along the entire gut. It is the pH measurement that provides our first way of examining fermentation in the intact colon. We propose to measure the pH profiles in the gut of 10 healthy volunteers and of 20 patients with UC who do not have active disease after both a large and a minimal load of indigestible, fermentable carbohydrates. This will be achieved by controlled food intake over the 12 hours prior to the capsule being swallowed. This will give us a range of pH profiles related to high and low levels of fermentation in the gut. We will then be able to determine if the fermentation capability of patients with UC is truly deficient. The pH-motility device will also permit us to examine transit through the regions of the gut and provide mechanistic information on the role of gut transit in any abnormalities found. We anticipate variation in responses of patients (but not in healthy volunteers). In order to be able to identify patients with abnormal fermentation, we will also collect, prior to the investigations with a wireless pH-motility device, dietary intake information and faeces to determine if these indices provide the correlations with the pH profile.

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