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.

Inclusion Criteria for Patients:

• Patients age between 5 and 70 years of age.
• Patients with IBS-D or IBS-M as defined by the Rome III criteria.
• Previous negative endoscopy with biopsies excluding IBD or microscopic colitis in patients above 50 years old
• Negative relevant additional screening or consultation whenever appropriate
• Ability to conform to the study protocol

Exclusion Criteria for Patients:

• Patients with IBS-C or IBS-U according to Rome III criteria
• Patients with any condition which, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
• Patients on opioids
• Patients with concurrent organic gastrointestinal disease (inflammatory bowel disease, celiac disease, cancer), or a major disease such as diabetes, uncontrolled thyroid disease
• Patients with a history of bowel surgery (not appendectomy or cholecystectomy)
• Concurrent major confounding condition, e.g. alcohol or substance abuse in the last 2 years (clinician's judgement).

Inclusion Criteria for healthy controls:

• Between 5 and 70 years of age
• Absence of Rome III IBS criteria

Exclusion Criteria for healthy controls:

• Blood relatives of the participating IBS patient are not allowed to participate.
• Person with any condition which, in the opinion of the investigator, makes them unsuitable for participation in the study.
• 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).

Multicentre study. IBS patients identified through secondary and tertiary care gastroenterological clinics.

Asymptomatic adult controls recruited at the same site as respective patients or, for instance, from transfusion clinics, blood donor centres, bowel cancer screening as long as data on the absence of symptoms is documented.