Lab-grown 'mini-guts' offer new insights for Crohn’s disease treatments

Crohn’s disease, which impacts about 1 in 350 people in the UK, varies greatly in severity among patients. The Cambridge team, led by Prof. Matthias Zilbauer, discovered that these mini-guts exhibit specific epigenetic changes that correlate with the severity of the disease. Unlike genetic mutations, epigenetic changes modify the DNA without altering its sequence, acting as "switches" that turn genes on or off. This discovery helps explain why the disease manifests differently in each patient, providing a foundation for more tailored treatment options. 

The research team utilized stem cells from the inflamed guts of 160 patients, primarily children and adolescents, to grow over 300 organoids. These 3D cell cultures replicate the gut's epithelial layer, providing a closer approximation of the human gut environment than previous models, which relied heavily on animal studies. 

One of the most significant findings from this research is the potential to use these organoids for testing and developing new treatments. Co-author Dr. Robert Heuschkel, Consultant Pediatric Gastroenterologist at Cambridge University Hospitals, emphasized the potential for these organoids to revolutionize treatment selection: " 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’.” 

The study highlighted a specific pathway involved in Crohn’s disease, known as the major histocompatibility complex (MHC)-I. This pathway is crucial for the immune system to recognize antigens, potentially leading to inflammation in the gut. The researchers found that in Crohn’s patients, the gut cells exhibited increased MHC-I activity, which could explain the localized inflammation observed in these patients. 

Another key finding was that the epigenetic changes observed in the mini-guts were remarkably stable, which could explain why inflammation often returns even after successful treatment. These stable changes may be set early in development and influenced by environmental factors, offering a possible explanation for the onset of Crohn’s disease. 

This research opens up new avenues for the development of personalized treatments for Crohn’s disease, potentially leading to more effective and targeted therapies. The study was supported by the Medical Research Council and the Milner Therapeutics Institute at the University of Cambridge. Cambridge Enterprise is now seeking commercial partners to further develop and commercialize this promising technology. 

MEDICA-tradefair.com; Source: University of Cambridge