Researchers Leverage 'Mini-Guts' to Advance Precision Medicine for Crohn's

New Research Sheds Light on Personalizing Crohn's Disease Treatment Using 'Mini-Guts'

Scientists at the University of Cambridge have made a significant breakthrough in understanding Crohn's disease, a debilitating form of inflammatory bowel disease (IBD). By growing "mini-guts" in the lab, researchers have discovered DNA changes that may play a crucial role in the condition, paving the way for more personalized and effective treatments.

Crohn's disease, which affects around one in 350 people in the UK, is a lifelong condition characterized by inflammation of the digestive tract. Symptoms can severely impact quality of life, including stomach pain, diarrhea, weight loss, and fatigue. Current treatments often involve extensive surgery, inpatient admissions, and exposure to toxic drugs.

Professor Matthias Zilbauer, a paediatric gastroenterologist at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust (CUH), explained, "The number of cases of Crohn's disease and IBD are rising dramatically worldwide, particularly among younger children, but despite decades of research, no one knows what causes it."

The researchers grew over 300 "mini-guts," also known as organoids, using cells from inflamed guts donated by 160 people, primarily patients and adolescents, as well as healthy individuals. These mini-organs, grown from stem cells, mimic the structure and function of the human intestine, allowing researchers to study the disease in greater detail.

One of the study participants, 11-year-old Arthur Hatt, who was diagnosed with Crohn's at the age of nine, donated some of his intestinal cells to the Translational Research in Intestinal Physiology and Pathology (TRIPP) study. "I think it's quite cool to be part of the study," Arthur said. "It's nice to know they're trying to get more information about Crohn's."

The study, published in the journal Gut, revealed that switches that modify DNA in gut cells play a significant role in the disease and how it presents in patients. These switches, known as epigenetic changes, are attached to DNA and can turn genes on or off, altering the way a cell functions without changing the DNA itself.

Importantly, the researchers found that these epigenetic changes correlated with the severity of the disease and were stable, which may explain why inflammation can return even after treatment when a patient appears to be healed.

"In the 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,'" said Dr. Robert Heuschkel, a consultant paediatric gastroenterologist at CUH and Lead of the Paediatric IBD Service.

The findings open up the possibility of tailoring treatments to individual patients, potentially allowing for more precise and personalized therapies. This could be a game-changer for patients like Arthur, who often struggle to find effective treatments and manage the debilitating symptoms of Crohn's disease.

The research, largely supported by the Medical Research Council and in collaboration with the Milner Therapeutics Institute at the University of Cambridge, represents a significant step forward in understanding and treating Crohn's disease, offering hope for improved quality of life for those living with this challenging condition.