Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis (GRAMPUS-CF) Strategic Research Centre
Many people with cystic fibrosis (CF) experience gut symptoms of CF on a daily basis. These can range from bloating and stomach cramps to intestinal blockages (the gut is also known as the intestines). The symptoms can prevent people with CF getting the calories they need, be extremely painful, embarrassing and disrupt day to day life. Current treatments for gut symptoms are often ineffective because doctors do not fully understand why symptoms occur.
In August 2022 Professor Alan Smyth from University of Nottingham began working with doctors and researchers from across the UK in a new Strategic Research Centre (SRC) funded by the Trust. They aim to link the specific symptoms people with CF experience to what changes are taking place within their intestines.
By increasing understanding of the cause of gut symptoms, the researchers hope that this could lead to more tailored medicines to treat people with CF in the future.
How will the researchers get the answers?
People with CF with gut symptoms in Nottingham and Leeds will be approached to take part in this study. If they agree they will report their symptoms using questionnaires, and then agree to undergo a series of hospital tests and donate samples for research. Looking at the results from the tests and what people said in their questionnaires, the researchers aim to link specific gut symptoms to changes seen within the intestines of people living with CF.
When these links have been made, other colleagues within the SRC will conduct lab studies to understand what triggers these changes to take place and investigate possible symptom-specific medicines that may be effective to treat them.
The Strategic Research Centre plan in more detail
More detail on the clinical (hospital-based) and laboratory based studies within this SRC are outlined below. The research costs £750,000 and will run for three years.
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Clinical Studies
To identify groups of people with CF with similar gut symptoms, the research group will ask 300 adults with CF and 50 children with CF to complete questionnaires about their symptoms. People with CF will be recruited from those attending CF clinics in Nottingham and Leeds. Based on the information provided, the team will use statistical techniques to separate these individuals into study groups according to their symptoms.
After everyone has completed the questionnaires, different sub-groups of participants will also be asked to take part in additional studies, giving blood or stool (poo) samples, and having MRI scans of their abdomen/intestines.
The blood samples will be used to study chemicals linked to gut inflammation. The type and number of bugs and the amount of fat within the stool samples will be analysed. The MRI scans will provide important information about how food moves through the intestines and data on the presence of inflammation by measuring physical changes to the thickness of the intestine lining.
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Laboratory studies
Microbiologists and biomedical co-investigators within the SRC will study the findings from the clinical studies in more detail, to confirm how and whether the changes seen are linked to CF using laboratory models. These lab models will then be used to screen for existing medicines that may repurposed to correct these changes.
The next step would be to test any potential beneficial medicines in clinical trials. Such clinical trials are beyond the remit of this Strategic Research Centre.
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Investigators
Investigators
Principal Investigator
Professor Alan Smyth, University of Nottingham & Nottingham NIHR Biomedical Research Centre.
Co-investigators
- Professor Luca Marciani, Nottingham Digestive Diseases Centre, University of Nottingham.
- Professor Robin Spiller, Nottingham Digestive Diseases Centre, University of Nottingham.
- Professor Penny Gowland, Sir Peter Mansfield Imaging Centre, University of Nottingham.
- Professor Tanya Monaghan, Nottingham Digestive Diseases Centre, University of Nottingham.
- Dr Niharika Duggal, Institute of Inflammation and Ageing, University of Birmingham.
- Professor Chris van der Gast, Manchester Metropolitan University.
- Dr Damian Rivett, Manchester Metropolitan University.
- Professor Daniel Peckham, University of Leeds.
- Dr Iain Stewart, Imperial College London.
Collaborators:
- Dr Richard Burchmore, University of Glasgow.
- Dr Helen Barr, Wolfson Adult CF Centre & Nottingham NIHR Biomedical Research Centre.
- Dr Katie Gathercole (person with CF)
- Dr Caroline Hoad, Sir Peter Mansfield Imaging Centre, University of Nottingham.
- Prof Jochen Mainz, Brandenburg Medical School, Germany.
- Dr Nick Markham, Vanderbilt University, Nashville, USA.
- Dr David Megson, Manchester Metropolitan University.
- Dr Alex Menys (Motilent Ltd).
- Dr Christos Polytarchou, Nottingham Trent University.
- Dr Fiona Whelan, School of Life Sciences, University of Nottingham.
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