Effects of FODMAPs on Small Bowel Water Content: an MRI Study

Overview

Some carbohydrates, particularly fructose, the sugar found in fruit and bread may cause bloating, pain and erratic bowel habits (diarrhoea and constipation) particularly in patients suffering from the irritable bowel syndrome (IBS). This may be because they are not well absorbed in the small intestine and cause water to be trapped in the bowel causing distension. Studies have shown that reducing the amount of these sugars in the diet can relieve these symptoms. There is some evidence that combining fructose and glucose can reduce the symptoms caused by fructose but just why is unclear. In this study, the investigators will use a non invasive medical imaging technique called "magnetic resonance imaging" (or MRI) to look at the behaviour of drinks containing these sugars in the bowels of healthy human volunteers. The investigators will give four different drinks: one beverage consisting of a very well absorbed sugar, glucose, another consisting of the less well absorbed sugar fructose, a third which is a mixture of glucose and fructose, and a fourth consisting of several fructose subunits joined together (called fructan). The investigators will take MRI images of the stomach and intestines at intervals for 5 hours and compare these with the feelings of distension and bloating in our volunteers. The results will act as control for subsequent studies in IBS patients and these may help design diets to reduce symptoms in IBS.

Title: Effects of FODMAPs (Fermentable Oligo-, Di-, and Mono-saccharides, And Polyols) on small bowel water content: an MRI study 1. Background. FODMAPs consist of fructose, lactose, fructo- and galacto-oligosaccharides such as fructans and galactans, and polyols such as sorbitol and mannitol. These carbohydrates are poorly absorbed in the small intestine and have been shown to trigger symptoms of irritable bowel syndrome (IBS). Previous studies have shown that fructose malabsorption results in an increased osmotic load in the small bowel, which can have a laxative effect. Physical proof of this has only been obtained using an ileostomy model on patients. This study indicated increased small bowel water content (SBWC) but this has never been established in intact humans .). We have been using noninvasive magnetic resonance imaging (MRI) to provide novel insights on the fate of food materials within the gastro-intestinal tract (GIT) of humans for the last decade. 2. Aims (to include hypothesis to be tested) This study aims to investigate whether fructose alone will increase SBWC compared to an equivalent mass of glucose, and if adding glucose to fructose will reduce its effect on the SBWC. The study also aims to determine if fructans alter colonic transit.The main hypothesis is that fructose will increase small bowel water while fructans will mainly affect colonic transit.. 3. Experimental protocol and methods. A single-centre, randomized, cross-over design study consisting of a screening visit and four test days, which will be approximately 1 week apart The subjects (18 healthy volunteers for main study plus 4 for pilot studies) will receive (according to a randomization schedule) each test day one out of four test products: 1) glucose (control) 2) fructose, 3) glucose with fructose and 4) fructans. On each test day, volunteers will have a baseline scan in a 1.5T scanner, consume one of the products instead of breakfast at 09:00 and will be imaged in the scanner at intervals for 5 hours using a range of MRI sequences. All the tested ingredients are food grade, have a history of safe use at intended usage levels, and are regarded as safe. Four test products will be evaluated: 1. 500 mL of glucose (40g of glucose dissolved in water with pure lime juice as flavorant) 2. 500 mL fructose (40g fructose dissolved in water with pure lime juice as flavorant) 3. 500 mL of glucose with fructose (40g glucose and 40g fructose dissolved in water with pure lime juice as flavorant, 40 or 80 gm) 4. 500 mL fructan (40g of 100% fructan (inulin) dissolved in water with pure lime juice as flavorant) 4\. Measurable end points/statistical power of the study. Primary endpoint: small bowel water content area under the curve (AUC) -45 - 315 minutes. Secondary endpoint: gastric emptying T50, colonic volume as characterised by AUC -45 - 315 minutes of ascending colon, colonic motility, symptoms questionnaires, small bowel transit time, breath hydrogen concentrations and tryptase faecal content. Previous work using mannitol and glucose indicates that mean (SD) SBWC at 40 minutes postprandial after ingesting 300ml glucose was 47 (SD 15) and using n=12 the investigators calculate the investigators can detect an increase of 20 ml in excess of this with 90% power which is very much less than the investigators are predicting. The investigators plan to use 18 to ensure the investigators can assess our secondary endpoints for which there is no data with which to perform a power calculation.