Imaging the Effect of Experimental Stress on Small and Large Bowel Water During Fructose Absorption

Imaging the Effect of Experimental Stress on Small and Large Bowel Water During Fructose Absorption

The investigators have been developing new, non-invasive magnetic resonance imaging (MRI) techniques to image the small bowel. Building on those studies the investigators want to study, in healthy volunteers, the effects of stress on the water content of the small bowel following ingestion of fructose. This is important because in Irritable Bowel Syndrome (IBS), there seems to be a strong association of stress and anxiety with the severity of the disease. Many IBS patients complain of food intolerances and recent studies have suggested that food with high content of fructose can worsen symptoms of IBS. The investigators will carry out a study in which the investigators will induce a moderate state of stress in healthy volunteers using an injection of corticotrophin release hormone, feed them a drink containing fructose and image their bowel at intervals using MRI. Improving our understanding of the effects of stress and fructose on small bowel physiology will help us to understand better some aspects of the symptoms such as bloating, altered bowel habit and abdominal discomfort, experienced by the IBS patients and to guide therapy. The investigators hypothesize that the effect of CRH will cause significant decrease in small bowel water content (SBWC) and a faster small bowel transit with increased malabsorption following consumption of fructose.

A single centre, randomized cross over study consisting a screening visit and 2 test days which will be approximately 7 days apart. The participants will receive 1g unlabelled lactose ureide in a glass of water 3 times a day on the day before the study day to induce the enzyme activity in the colonic bacteria. The participants (20 healthy volunteers) will have a baseline scan in a 1.5T MRI scanner before having a small intravenous needle inserted into their forearm. Following this procedure, the participant will have another scan before being given either a saline (0.9% NaCl) or 100microgram of CRH intravenous injection. 40g of fructose and 500mg of labeled C-13 lactose ureide dissolved in water with pure lime juice as flavorant made up to 500mL will be given to the participants. They will then have a serial scanning of the abdomen at 30-60 minutes interval for 5 hours post prandially. Salivary cortisol will be collected after every MRI scans. Participants will also be asked to blow into the hydrogen breath machine and to fill in symptom questionnaire following each MRI scans. Further breath collections for orocaecal transit time will be collected initially every 10 minutes for the first hour and 15 mins until the end of the study day. Mouthwash will be used before initial breath test collection. This procedure will be repeated again on the 2nd test day with either a saline or 100microgram of CRH.

Inclusion Criteria:

• Male or female healthy volunteers who are 18-60 years old
• Age ≥ 18 and ≤ 60 year at pre-study investigation.
• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2
• Able to give voluntary informed consent to participate in the study
• Able to understand the requirements of the study including anonymous publication and free to cooperate with the study procedures

Exclusion Criteria:

• Lactose intolerance
• Any history of serious acute or chronic illness especially gastrointestinal
• Any history of Raynaud's syndrome or impairment of circulation
• Any history of heart or lung disease
• Pregnancy or breastfeeding
• Smoking
• Unsuitable for MRI scanning (i.e. have metal implants or pacemaker)
• Regular medication interfering with gastrointestinal function, opiates or constipating drugs
• Substance abuse
• Have taken part in any other clinical study within the previous 3 months
• Previous gastrointestinal surgery
• Use of medication which interferes with study measurements or bowel motility (as judged by the study physician) such as antibiotics in the 2 weeks before pre-study examination or probiotics.