genetic carbohydrate maldigestion as model to study food hypersensitivity mechanism (work package 2)

Conditions: Sucrase Isomaltase Deficiency

Summary: 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.


Eligibility criteria:
inclusion criteria for csid subjects: * 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) * ability to conform to the study protocol including the sucrose challenge. exclusion criteria for csid subjects: * 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 * having taken part in another interventional research study within 3 months * concurrent major confounding condition (e.g. alcohol or substance abuse in the last 2 years) based on the study clinician's judgement. inclusion criteria for healthy participants: * aged ≥18 years * absence of rome iii ibs criteria * non-si variant confirmed (group 1) or single-si variants confirmed (group 2) or double - si variants confirmed (group 3) * ability to conform to the study protocol including the sucrose challenge exclusion criteria for healthy participants: * person presenting with a functional or organic gi disorder. * person presenting with underlying disease that may involve the gi tract (e.g. parkinson's disease) or be associated with gi symptoms (e.g. anorexia nervosa, major depression). * any history of bowel surgery (not appendectomy or cholecystectomy) * contraindication to mri scanning * having taken part in another interventional research study within 3 months * concurrent major confounding condition (e.g. alcohol or substance abuse in the last 2 years) based on the clinician's judgement.

Keywords: sucrose isomaltase deficiency