Clinical Research Directory

Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity

Irritable bowel syndrome (IBS) affects one in seven people with gastrointestinal (GI) symptoms. 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) (1). The development of therapeutic options is hampered by the poor understanding of the underlying cause of symptoms. Many patients find that certain foods (particularly carbohydrates) trigger their symptoms, and avoiding such foods has been shown effective in IBS, like in the low-FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) exclusion diet. This has suggested that the food-symptom relation may involve malabsorption of carbohydrates due to inefficient digestion. However only a percentage of patients respond to this diet. Recently it has been reported that a subset of IBS carries hypomorphic (defective) gene variant of the sucrase isomaltase (SI), the enzyme that normally digests carbohydrates, sucrose and starch. This carbohydrate maldigestion (the breakdown of complex carbohydrates by a person's small bowel enzymes) is characterized by diarrhoea, abdominal pain and bloating, which are also features of IBS. This possibly occurs via accumulation of undigested carbohydrates in the large bowel, where they cause symptoms due to gas production following bacterial fermentation. Similar mechanisms may be acting at the level of other enzymes involved in the digestion, breakdown and absorption of carbohydrates (carb digestion genes -CDGs). Aim of the study is to study the prevalence of this genetic alteration in a large number of IBS patients as compared to asymptomatic controls.

Genetic Carbohydrate Maldigestion As Model to Study Food Hypersensitivity Mechanism (WORK PACKAGE 2)

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.

Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional disorder causing troublesome symptoms and reduced quality of life. It affects 10-20% of the population, hence creates large costs for society. About 30-40% of all IBS patients do not benefit from current treatment options. Sucrase-isomaltase (SI) deficiency is an unexplored condition, that may explain symptoms in IBS patients who experience no effect from today's treatments. Currently, a duodenal biopsy is the gold standard for the diagnosis of SI deficiency, however the condition is not well investigated. A 13C-labelled breath test holds promise as a non-invasive alternative, but it has not previously been validated. This project will address the knowledge gap related to a possible association between SI deficiency and IBS by addressing two research questions that have never been answered before. We aim to: 1. Validate the 13C-labelled breath test as a diagnostic tool by assessing the strength of the association between the breath test and SI activity measured in duodenal biopsies 2. Use the 13C-labelled breath test in a randomized dietary crossover trial comparing a starch and sucrose reduced diet (SSRD) with the standard low-FODMAP diet in IBS patients, to evaluate whether SI activity is associated with dietary changes according to symptom severity and gut microbiota composition