GENETIC CARBOHYDRATE MALDIGESTION AS A MODEL TO STUDY FOOD HYPERSENSITIVITY MECHANISM AND GUIDE PERSONALISED TREATMENT USING A NON-INVASIVE MULTIPARAMETRIC TEST
It is estimated that about 20% of the population has a food intolerance and that in people with Irritable Bowel Syndrome (which affects about 1 in 10 people in the UK), food intolerance is even higher.
A new international research study, co-ordinated from the UK and involving patients from across the world aims to investigate whether there is a genetic reason for this and what new therapies could be developed to treat the symptoms.
About the project
Members of the GenMalCarb team have shown that compared to healthy people, IBS patients more often carry defective (hypomorphic) SI gene variants. The SI gene produces an enzyme, called sucrase-isomaltase, which is used by the body to digest carbohydrates such as starch and table sugar (sucrose).
These results suggest that a sub-group of IBS patients, if correctly identified, could benefit from personalised treatments using dietary interventions or enzyme supplementation.
In order to develop specific treatments, researchers need to understand the exact mechanisms which lead to symptoms as a result of carbohydrate maldigestion. The GenMalCarb study, which is led by experts from the Univesrity of Nottingham, will use a magnetic resonance imaging (MRI) platform that allows the analysis of gut responses to food in real time. The research team will use this platform to study carbohydrate maldigestion in IBS patients carrying hypomorphic SI variants. The study will be run in collaboration with international research teams.
What this research aims to discover
The GenMalCarb project aims to:
- accurately establish how many IBS patients carry DNA changes predisposing to SI malfunction in an international study involving more than 30 centres worldwide (Work Package 1)
- confirm SI dysfunction (reduced capacity to digest sucrose and starch) for all identified hypomorphic variants via experimental validation in cell-based models (Work Package 1)
- Elucidate via MRI studies what part of the digestive process is dysfunctional in IBS patients carrying different SI variants, in response to ingestion of carbohydrate (Work Package 2)
How this study will help patients
For many people with IBS, eating carbohydrates triggers symptoms such as stomach cramps, bloating, diarrhoea and constipation. These tend to come and go over time, and can last for days, weeks or months at a time. These symptoms are often regarded as the result of psychological responses to certain foods.
The GenMalCarb study will take a different approach to try and elucidate the molecular mechanisms behind these symptoms. They will combine genetic profiling of multiple patients with MRI technology in selected cases to understand what happens when people with a defective SI gene eat carbohydrates. The study will examine results from patients across 30 centres across the world.
The results from this research will open up the possibility for new personalised therapies, based on tailor-made dietary treatments and enzyme supplementation.
Working with patients
The Patient & Public Involvement Advisory Group which supports the Gastrointestinal and Liver Theme of the the NIHR Nottingham Biomedical Research Centre is working with patients to support the set up of this study in Nottingham. If you would like to get involved then please contact Andrew Wragg, Patient and Public Involvement lead for this study.
For more information
This study is led by Dr Maura Corsetti, University of Nottingham, in collaboration with an international team of experts:
- Professor Mauro D’Amato, CIC bioGUNE, Bilbao, Spain
- Professor Andre Franke, Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Professor Naim Hassan, Institute for Biochemistry, University of Veterinary Medicine, Hannover, Germany
The Nottingham Team responsible for Workpackage 2 includes: