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

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.

Conditions

• Sucrase Isomaltase Deficiency

Interventions

OTHER

Blood, stool and saliva collection

Blood, stool and saliva collection

OTHER

Questionnaire completion

Questionnaire 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

DIAGNOSTIC_TEST

Magnetic Resonance Imaging (MRI) and Breath test

MRI scans and breath test samples collected after drink test with sucrose

Sponsors & Collaborators

• cic bioGune

  collaborator UNKNOWN

• Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel

  collaborator UNKNOWN

• University of Veterinary Medicine Hannover

  collaborator UNKNOWN

• University of Nottingham

  lead OTHER

Principal Investigators

• Maura Corsetti, Medical Doctor · University of Nottingham

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-03-31

Primary Completion

2025-12-31

Completion

2026-03-31

Countries

• United Kingdom

Study Locations