A Living Organoid Biobank of Crohn’s Disease Patients Reveals Distinct Clinical Correlates of Molecular Disease Subtypes.

Doctors caring for people with Crohn’s disease often struggle to predict how the illness will behave over time because current laboratory models do not accurately reflect the complexity of real patients. To address this gap, the study uses patient-derived organoids—tiny, lab-grown replicas of a person’s intestinal tissue—to create a new kind of predictive model for Crohn’s disease. Using a large collection of organoids grown from adult colon stem cells, we previously identified two distinct molecular subtypes of Crohn’s disease. One subtype, called IDICD, shows signs of impaired immune defense and increased susceptibility to infection. The other, S2FCD, shows features of cellular stress, aging, and scarring (fibrosis). Each subtype responds differently to therapies in the lab. In this study, we linked these organoid-based profiles to real patient outcomes. They found that people whose organoids fall into the S2FCD category are more likely to have inflammation and worsening disease activity in the colon. In contrast, those matching the IDICD subtype tend to have had prior surgery in the ileocecal region (where the small and large intestine meet), show more penetrating or aggressive disease behavior, and have inflammation in the ileum. By developing organoid models that mirror actual patient histories and future disease patterns, this work shows that these miniature tissues can serve as powerful tools for predicting disease progression and guiding treatment decisions. Beyond their growing use in cancer research, organoids now show promise as platforms for clinical trial–like studies in inflammatory diseases. The findings also suggest that problems in the colon’s immune system may play a key role in driving Crohn’s disease in the ileum.