Scientists grow ‘mini-guts’ to study Crohn’s disease

Scientists have grown “mini-guts” in the lab to help understand Crohn’s disease, and discovered DNA changes that may play an important role in the condition.

Cambridge University researchers say that these tiny organs – also known as organs – could be used in the future to identify the best treatment for an individual patient, allowing for more precise and personalized treatments.

About one in 350 people in the UK has Crohn’s disease – and one in four presents before the age of 18. It is a type of inflammatory bowel disease (IBD).

It is a lifelong condition characterized by inflammation of the digestive tract.

Symptoms can have a significant impact on quality of life and include stomach pain, diarrhoea, weight loss and fatigue, and can also lead to extensive surgery, inpatient admission and exposure to toxic drugs.

Matthias Zilbauer, professor of pediatric gastroenterology at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust (CUH), said: “The number of cases of Crohn’s disease and IBD is increasing dramatically worldwide, particularly among younger children, but despite years of research. , no one knows what causes it.”

He added: “The organs we have generated are mainly from children and teenagers.

“They basically gave us pieces of their gut to help with our research.”

Arthur Hatt, 11, was diagnosed with Crohn’s at the age of nine, but according to his mother Sian Hatt, he had been showing symptoms from a very young age.

Arthur is one of the children who took part in the Translational Research into Intestinal Physiology and Pathology (TRIPP) study at the University of Cambridge.

He donated some of the cells from his intestine, which Professor Zilbauer and his colleagues are now using to grow a ‘mini-intestine’ to better understand Crohn’s disease.

He said: “I think it’s really cool to be part of the study.

“It’s nice to know they want to know more about Crohn’s.”

In a message to other children with the condition, he said: “There are bad days and there are good days, but eventually you will find the right medicine.

“Sometimes it can take a long time, but eventually they will find what works for you.”

Using the mini-intestines, the researchers also discovered that switches that change DNA in gut cells play an important role in the disease and how it presents in patients.

These switches are attached to DNA that turn genes on and off – or turn their activity up or down – leaving the DNA itself intact, but changing how a cell functions.

The study found that there was a correlation between these changes in Crohn’s patients and the severity of the disease.

Professor Zilbauer, a researcher at the Stem Cell Institute at the University of Cambridge, said: “Each patient’s disease course is different, and these changes help to explain why – not all organisms had the same epigenetic changes.”

In the new research, published in Gut, the researchers used cells from inflamed intestines, donated by 160 people, mainly patients and adolescents, but also healthy people, at CUH to grow more than 300 mini-intestines.

The researchers say the mini-guts open up the possibility of tailoring treatments to individual patients.

Co-author Dr Robert Heuschkel, consultant pediatric gastroenterologist at CUH and Head of the Pediatric IBD Service, said: “In the future, you could imagine taking cells from an individual patient, growing them in their organelles, testing drugs different on the organoid, and you say, ‘Okay, this is the drug that works for this person’.”

​​​​The study also found that the DNA changes were stable, which could explain why even after treatment, when a patient seems to be cured, their inflammation can return after some months – the drugs treat the symptoms, not the root cause.

In the future, the results could help patients like Arthur access effective treatment more quickly.

Ms Hatt said before Arthur was diagnosed they were told he had toddler diarrhoea, food intolerances and even abdominal migraines.

Eventually, the youngster was diagnosed at the age of nine, and was prescribed the drug azathioprine, which he is still on today.

Because it could take a long time for the effects of the medication to work, he was also temporarily prescribed steroids, but Arthur said: “They made me feel great and I was very hungry.”

Miss Hatt said there were times when Arthur was only able to attend school for half days, and even now holidays are usually about rest, with the youngster particularly suffering during the off-season. colds and flu, as the treatments tend to suppress the immune system. system.

However, Arthur still manages to do the things he likes.

Arthur said: “I love dancing, especially Latin and street dancing.

“I get to do most of the things I like to do, but sometimes I get tired.”

The research was largely supported by the Medical Research Council, and was also supported by a collaboration with the Milner Institute of Therapeutics, University of Cambridge.

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