Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity Mechanism and Guide Personalised Treatment Using a Non-invasive Multiparametric Test (Work Package 1)

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.