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What did the project achieve?
“Overall, it is increasingly clear from this project that Crohn’s disease occurs due to specific genetic or environmental causes that are likely to be individual to each child, or family,” says Dr James Ashton of the University of Southampton. “We believe that some of our findings could help in the diagnosis and treatment of more children with Crohn’s disease in the near future – enabling doctors to use genetic information to personalise care for each patient.”
Crohn’s disease is an inflammatory disease that mainly affects the gut. Young people affected with the condition will experience a range of debilitating symptoms such as diarrhoea, abdominal pain and weight loss – as well as unique emotional and social challenges. But it is unclear what triggers the inflammation and unfortunately, it can take time to find the best treatment for each child, during which their condition may worsen or complications arise.
The goal of this project was to improve understanding of the causes of the disease – and to use this information to predict how severe a child’s illness will be and how well they will respond to treatments. The team analysed samples from around 350 children with Crohn’s disease at diagnosis – and combined these data with clinical information about the progression of their condition.
“The most important and clinically relevant finding was the identification of a precise genetic diagnosis in 8% of the children, showing specific and new gene changes and inflammatory pathways that may be involved in the development of the disease,” says Dr Ashton. “We have taken the first steps towards personalised medicine in this group of children – and we now plan to investigate one of the genes, NOD2, and to build a clinical tool to help doctors predict the risk of developing a potentially serious complication where parts of the intestine become narrowed.”
The researchers now hope to continue to follow up on 50 patients throughout childhood to find out if it is possible to use the data from samples collected at diagnosis to predict longer-term disease outcomes.
In another part of the project, the team used a cutting-edge new technique to analyse the activity of a set of genes (which are involved in triggering the body’s immune system to mistakenly attack its own tissues) in the gut of children with Crohn’s disease.
“We identified a specific pattern of gene activity in a child’s gut that appears to increase their risk of experiencing an early relapse, which could ultimately lead to a test that can help doctors to identify who may benefit from receiving more aggressive treatment sooner,” says Dr Ashton.
The hope in the longer term is that many more patients will benefit from this work – by understanding how individual patients respond to treatment, and how to personalise treatment to reach the best outcomes for each child affected by Crohn’s disease.
This research was completed on
Research Training Fellowship*: Dr James Ashton
At least 115,000 people have Crohn's disease in the UK.1 Up to one third are young – less than 21 years old – when their condition is diagnosed.1 Children with Crohn’s disease can experience symptoms, such as diarrhoea, abdominal pain and tiredness, which result from inflammation in the gut, but it’s unclear what triggers this inflammation. Dr James Ashton, of the University of Southampton, aims to improve understanding of what causes Crohn’s disease. His work may one day lead to better treatments and improved quality of life for children and young people with this debilitating condition.
How are children’s lives affected now?
More and more children are being diagnosed with Crohn’s disease, an incurable condition that primarily affects the gut.2-4
The condition is unpredictable. Children have periods of time with very mild symptoms or no symptoms, followed by times when their symptoms flare up and become particularly bad.
“Children with Crohn’s disease tend to have more severe symptoms than adults,” says Dr Ashton. “The condition can have a significant impact on children’s lives – for example, their growth, schooling and psychological wellbeing can all be affected.” Symptoms can affect children’s self-esteem, relationships and social lives.
Medication and nutritional therapy can help, but many children with Crohn’s disease have to undergo surgery within 10 years of diagnosis to remove damaged parts of the bowel.5
“A lack of understanding of what causes Crohn’s disease is hindering efforts to develop better treatments and use the treatments we have effectively,” says Dr Ashton. “More research is needed urgently.”
How could this research help?
“We are investigating what triggers Crohn’s disease, and its flare ups, in children,” says Dr Ashton. No-one knows exactly what causes the condition, but it’s thought that a combination of genetic and environmental factors are involved.
Dr Ashton is studying the role the microbiome plays in triggering disease. The microbiome is the community of bacteria that live in the gut. He is also assessing how this community of bacteria might interact with two other factors to cause disease. One is the children’s genetic susceptibility to developing Crohn’s disease (which depends on which genes they have). The other is the activity of the children’s immune system (which can change if genes are turned on or turned off).
“We hope that our findings will help in the development of better ways to predict disease severity, as well as new and improved treatments, with the ultimate goal of improving children’s lives,” says Dr Ashton.
References
1. National Institute for Health and Clinical Excellence (NICE). Crohn’s disease: management. Last updated May 2016. https://www.nice.org.uk/guidance/cg152/chapter/Context Website accessed 21 March 2017.
2. Ashton JJ et al. Rising incidence of paediatric inflammatory bowel disease (PIBD) in Wessex, Southern England. Arch Dis Child 2014; 99: 659-664.
3. Hope B et al. Rapid rise in incidence of Irish paediatric inflammatory bowel disease. Arch Dis Child 2012; 97: 590-594.
4. Henderson P et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm Bowel Dis 2012; 18: 999-1005.
5. The Inflammatory Bowel Disease (IBD) Standards Group. Standards for the Healthcare of People who have Inflammatory Bowel Disease (IBD). IBD Standards 2013 Update. Website accessed 3 April 2017.
* Research Training Fellowships:
Each year, Action Medical Research awards these prestigious grants to help develop some of the UK’s brightest doctors and scientists as future leaders in children’s research.
| Project Leader | Dr James J Ashton BMedSci BMBS MRCPCH |
| Project Team | Professor Sarah Ennis BSc PhD FHEAProfessor R Mark Beattie BSc MBBS FRCPCH |
| Project Location | Human Development and Health, University of Southampton |
| Project Location Other | Department of Paediatric Gastroenterology, Southampton Children's Hospital |
| Project duration | 3 years |
| Date awarded | 14 February 2017 |
| Project start date | 6 September 2017 |
| Project end date | 1 March 2021 |
| Grant amount | £240,640 |
| Grant code | GN2560 |
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