Irritable bowel syndrome (IBS) affects one in seven people with gastrointestinal (GI) symptoms that are detected without an established underlying organic cause. IBS strongly impacts quality of life, is a leading cause of work absenteeism, and consumes 0.5% of the healthcare annual budget. It manifests in women more than men with symptoms including abdominal pain, bloating, constipation (IBS-C), diarrhoea (IBS-D), and mixed presentations (IBS-M). The development of therapeutic options is hampered by the heterogeneity of IBS, the lack of specificity of its symptom-based definitions, and the poor understanding of the underlying pathophysiological mechanisms.
Many people with IBS find that certain foods (particularly carbohydrates) trigger their symptoms and avoiding such foods has been shown to be effective in IBS. An example of such a diet is the low-FODMAP (fermentable oligo-, di-, monosaccharides and polyols) exclusion diet, developed by researchers at Monash University. This has suggested that the food-symptom relation may involve malabsorption of carbohydrates due to inefficient enzymatic breakdown of polysaccharides. However, only a percentage of subjects respond to this diet. Overall, the current findings relating to SI, suggest a strong potential for effective personalized therapeutic (dietary) interventions in subgroups of IBS subjects and suggest similar mechanisms should be investigated in relation to other genes involved in the digestion and absorption of carbohydrates (CDGs). This project aims to understand what the mechanisms for GI symptoms in subjects with these genetic alterations are. Aim of the study is to assess the gut response to a sucrose challenge in single-and double-carriers of the common hypomorphic sucrase-isomaltase variant p. (Val15Phe) vs non- carriers (negative controls) and CSID subjects (positive controls), applying an MRI multiparametric test combined with a breath test.
Aged ≥18 (all groups)
Subjects with genetically proven CSID
Previous negative endoscopy with biopsies excluding IBD or microscopic colitis in people above 50 years old.
Negative relevant additional screening (including exclusion of coeliac disease with TTG and IgA)
Subjects on opioids and use of drugs known to alter GI motility for the duration of the study.
Presence of concurrent organic gastrointestinal disease (inflammatory bowel disease, coeliac disease, cancer), or a major disease such as diabetes, uncontrolled thyroid disease
Any history of bowel surgery (not appendectomy or cholecystectomy)
Contraindication to MRI scanning
Single-centre study. CSID subjects will be identified and recruited either with the help of the PPI group through advertisements on social media or flyers at Clinical Genetics and Genomic Conferences and Adult Metabolic Disorder Conferences. Healthy participants will be recruited through social media advertisements and posters.
Case-control
Prospective
Blood, stool and saliva collection
Other interventionBlood, stool and saliva collection
Questionnaire completion
Other interventionQuestionnaire on: * Hospital Anxiety and Depression Score (HADS) for adults * Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by CNAQ questionnaire for adults and children * Patient Health Questionnaire 12 (PHQ-12) Somatic Symptom scale
Magnetic Resonance Imaging (MRI) and Breath test
Diagnostic testMRI scans and breath test samples collected after drink test with sucrose
Area under the curve
Area under curve (AUC) of the change from baseline for the MRI measured small bowel water content after the drink test with sucrose
Habitual diet questionnaire
subject will report food eaten at each meal
MRI measured colon free water content
MRI measured colon free water content, (in arbitrary units) after the drink test
MRI measured small bowel and colon gas content
small bowel and colon gas content (in arbitrary units) after the drink test
MRI measured small bowel and colon volume
small bowel and colon volume in arbritary units after drink test
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University of Nottingham
Lead sponsor
cic bioGune
Collaborator
Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel
Collaborator
University of Veterinary Medicine Hannover
Collaborator
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