Dr Miriam Stoppard on the creation of ‘mini organs’ to help us understand complex inflammatory bowel conditions such as the debilitating Crohn’s disease
One of the exciting ways diseases can be studied is to create “mini” organs in the lab, instead of having to experiment on a person.
The latest lab-grown mini-guts have been helping us understand complex conditions such as Crohn’s disease (CD), a debilitating inflammatory bowel condition. Cambridge scientists even believe their mini guts could identify the best treatment for an individual patient, providing them with more precise and personalised care.
CD is a lifelong condition causing inflammation of the digestive tract that affects around one in 350 people in the UK, with one in four before the age of 18. Even at its mildest, symptoms can include stomach pain, diarrhoea, weight loss and fatigue. But it can also lead to extensive surgery, exposure to toxic drugs and admissions to hospital, which have a major impact not only on a patient but also their families. There’s some evidence a person is at greater risk of developing Crohn’s if a first-degree relative has it, so might there be a gene at work? Could be.
Professor Matthias Zilbauer, of Cambridge University, points out: “The number of cases of Crohn’s disease and inflammatory bowel disease are rising dramatically worldwide, particularly among younger children, but despite decades of research, no one knows what causes it.”
Prof Zilbauer and colleagues used cells from inflamed guts donated by 160 patients to grow more than 300 mini guts, known as organoids, in the lab. These patients – mainly children and adolescents – literally gave the researchers pieces of their bowel to help with their research.
The organoids showed the lining of the guts of Crohn’s disease patients have different patterns on their DNA compared to healthy ones. These turn genes on and off – or turn their activity up or down – leaving the DNA itself intact, but changing the way a cell functions. Scientists also found a correlation between these “epigenetic” changes, and the severity of the disease.
Researchers say the organoids could be used to develop and test new treatments and see how effective they are on the gut’s lining in CD, also tailoring treatments to individual patients. Co-author Dr Robert Heuschkel, of Cambridge, 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.” Prof Zilbauer added: “This is the first time where anyone has been able to show that stable epigenetic changes can explain what is wrong in the gut in patients with Crohn’s.”