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Children help scientists grow 'mini-guts' to help treat Crohn's disease

Children have been helping Cambridge scientists grow 'mini-guts' in the lab to understand more about Crohn's disease, allowing for more personalised treatments to individual patients in the future.

A boy smiling wearing a multi-coloured hat

Arthur Hatt, aged 11, is one of the children taking part in the Translational Research in Intestinal Physiology and Pathology (TRIPP) study at the University of Cambridge, which is aimed at understanding our gut health.

He was diagnosed with Crohn's at the age of nine, but his mother Sian says that in hindsight, he was showing symptoms from a very early age.

"From the age of about 12 to 18 months, he was having problems with his tummy – loose stools all the time and lots of stomach pains," she says.

Crohn’s disease is a form of inflammatory bowel disease (IBD). It is a life-long condition characterised by inflammation of the digestive tract that affects around one in 350 people in the UK, with one in four presenting before the age of 18.

By growing 'mini-guts' in the lab, University of Cambridge scientists have discovered that DNA changes in gut cells play and important role in how the disease presents in patients. This could in the future be used to identify the best treatment for individual patients.

Embedded inside the planned Cambridge Children's Hospital will be a state-of-the-art Cambridge Children's Research Institute (CCRI), bringing researchers and clinicians together with world-class biomedical research organisations and industry partners. By co-locating the Institute within the hospital, it will accelerate the translational benefits of studies like this, to many more children and young people to detect disease early, or prevent it altogether, and personalise healthcare.

It's quite cool to be part of the study. It’s nice to know they're trying to get more information about Crohn’s.

Arthur Hatt

Arthur was referred to Addenbrooke’s Hospital, where he was seen by Professor Matthias Zilbauer, Professor of Paediatric Gastroenterology at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust (CUH). Professor Zilbauer said: "The number of cases of Crohn’s disease and IBD are rising dramatically worldwide, particularly amongst younger children, but despite decades of research, no one knows what causes it."

In research published today in Gut, Professor Zilbauer and colleagues used cells from inflamed guts, donated by 160 patients, mainly patients and adolescents, at CUH to grow more than 300 mini-guts – known as organoids – in the lab to help them better understand the condition. Samples were donated by patients with Crohn’s disease and ulcerative colitis, including Arthur who donated some of the cells from his intestine, as well as by patients unaffected by IBD.

A mini gut
Mini-guts, known as organoids. Credit: University of Cambridge

"The organoids that we've generated are primarily from children and adolescents," said Professor Zilbauer. "They’ve essentially given us pieces of their bowel to help with our research. Crohn’s can be a severe condition to have to deal with at any age."

These days, more and more children are being diagnosed with Crohn’s disease and IBD. To these children, Arthur has a message:

There are bad days and there are good days, but eventually you'll find the right medicine. Sometimes it can take a really long time, but eventually they’ll find the thing that works for you.

Arthur, aged 11

Using the mini guts the researchers found that 'switches' which modify DNA in gut cells - by turning genes on and off or turning their activity up or down - leaving the DNA itself intact, changes the way a cell functions. The scientists discovered these changes were different in patients with Crohn's disease, and there was a correlation between the changes and the severity of the disease.

They found every patient's disease course is different, and this plays an important role in the disease and how it presents in patients. It also opens up the possibility of tailoring treatments to individual patients.

Co-author Dr Robert Heuschkel, Consultant Paediatric Gastroenterologist at CUH and Cambridge Children’s Hospital Clinical Lead for Physical Health said: "At the moment, we have no way of knowing which treatment will work best for a patient. Even those treatments we currently have only work in around half of our patients and become less effective over time. It's a huge problem."

Dr Rob Heuschkel, Clinical Director for Cambridge Children’s Hospital Project,  Cambridge University Hospitals NHS Foundation Trust (CUH)
Dr Robert Heuschkel

In future, you could imagine taking cells from a particular patient, growing their organoid, testing different drugs on the organoid, and saying, ‘OK, this is the drug that works for this person

Dr Robert Heuschkel

These findings also mean children like Arthur could access treatment more quickly in the future.

Arthur was prescribed the drug azathioprine, which he is still on to this day. Because it can take time for the effects of the medication to work, he was also temporarily prescribed steroids. Azathioprine by itself has not been enough to fully control his symptoms, so he has had to try several other medications. He is also receiving infliximab, which is given via infusion at Addenbrooke’s.

The drugs do, however, come with side-effects. Azathioprine, for example, can make the skin more sensitive to light, so Arthur has to wear sunscreen whenever he goes outside. The treatments also tend to suppress the immune system, leaving him more susceptible to infections.

A boy wearing a hat and smiling
Arthur Hatt

Although Arthur is back at school full time now, there have been long periods where he was only able to manage half days.

Fortunately, Arthur still manages to do the things he enjoys. He enjoys performing and dancing, especially Latin and street dance.

"I manage to do most of the things I like, but I get tired sometimes."

The research was largely supported by the Medical Research Council, in collaboration with the Milner Thereaptics Institute, University of Cambridge.

To learn more about Arthur's story and the 'mini-guts' study visit the University of Cambridge's website here. (opens in a new tab)