Small and Large Bowel Transit Tests Using MRI (Study 1)

Irritable bowel syndrome, (IBS) is a common functional disorder of the gut that can be quite disabling to patients. The most common symptoms of IBS are abdominal pain or discomfort along with erratic changes in bowel habit of diarrhoea, constipation or a mixture of the two (referred to as IBS subtypes). Despite much research efforts to further understand the pathophysiology of IBS; as yet no specific biomarkers/definitive measurements have been identified that can be use to aid the diagnosis and reduce the need for unnecessary, unpleasant and expensive tests.

Evidence shows that anxiety plays a part in IBS and can speed up transit time in the small bowel. In this study, the investigators hypothesise that since anxiety is a common feature of IBS, then fast small bowel transit is likely to be found in all subtypes of IBS and the difference in stool frequency and consistency in IBS subgroups are therefore likely to reflect differences in colonic function. The investigator wish to test this by measuring both small and large bowel transit times using Magnetic Resonance Imaging (MRI) and validate the results of the MRI with two methods currently used in clinical practice -The previously validated lactose-C13 Ureide breath test (for small bowel transit) and the standard radio-opaque pellet method to assess the whole gut transit (WGT) time.

The investigator has 2 main parts in this study i.e. Study 1 and Study 2.

As part of study 1, the investigator would like to recruit up to 5 healthy volunteers as a pilot study to optimise measurement and analysis of the Lactose-C13 Ureide breath test along with MRI scannings at regular intervals.

Following from this, the investigator would like assess the feasibility and reproducibility of using MRI imaging to assess gastrointestinal transit. The investigator would like to recruit 21 healthy volunteers to measure orocaecal transit time (OCTT) and whole gut transit(WGT)using the conventional method of Lactose-C13 Ureide breath test for OCTT and the Metcalf method using standard radio-opaque pellet method for WGT and compare them will MRI imaging. Once this has been analysed and the best method for each OCTT and WGT have been decided, these methods would be applied in Study 2.

In study 2, the investigator would like to recruit 30 healthy volunteers, 30 patients with diarrhoea predominantly Irritable Bowel Syndrome, 30 patients with constipation predominantly Irritable Bowel Syndrome and 30 patients with Mixed irritable Bowel Syndrome. The best methods from study 1 for OCTT and WGT will be applied here to assess gastrointestinal transit on these subjects. Based on the first study, the best method to assess OCTT is the Lactose-C13 Ureide breath test and for the WGT, the best method is the MRI marker capsules. Participants will need to fill in questionnaires to assess their stress levels and to fill in symptom questionnaires during the study day.

Eligibility Criteria:
Study 1

Inclusion Criteria

* 26 healthy volunteer
* Age 18-75 years old
* Non-smoker
* Able to give informed consent

Exclusion Criteria

* Lactose intolerant
* Any history of gastrointestinal surgery on the small bowel (excluding appendicectomy)
* Pregnancy
* contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury alcohol dependence
* serious concomitant illness as judged by the investigators
* use of drugs known to alter GI motility including opiates, anti-depressants, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test
* inability to lie flat or exceed scanner limits of weight \>120kg or abdominal circumference \>99cm ; BMI \<18 and \>30 kg/m2
* Poor command of English language
* Participation of any medical trials for the past 3 months

Study 2:

120 participants consisting of: 30 patients with diarrhoea predominant IBS according to Rome III criteria 30 patients with constipation predominant IBS according to Rome III criteria 30 patients with mixed type IBS according to Rome III criteria 30 healthy volunteers age and sex matched controls

Inclusion criteria

* Meet the Rome III criteria and the IBS subtypes
* Age 18-75 years old
* Able to give informed consent
* Subjects will undergo a limited screening medical. They will also complete a MRI - safety questionnaire and be given an information sheet
* Able to give informed consent
* Subjects will undergo screening medical questionnaire. They will also complete a MRI safety questionnaire and be given an information sheet

Exclusion Criteria

* Any history of gastrointestinal surgery on the small bowel (excluding appendicectomy)
* Pregnancy
* contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
* alcohol dependence
* serious concomitant illness as judged by the investigators
* use of drugs known to alter GI motility including opiates, , monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test
* Selective serotonin reuptake inhibitors or low dose tricyclic antidepressants will be recorded but will not be an exclusion
* No recent antibiotic treatment past 2 weeks
* inability to lie flat or exceed scanner limits of weight \>120kg or abdominal circumference \>99cm; BMI \<18 and \>30 kg/m2
* Poor command of English language
* Participation of any medical trials for the past 3 months