Scientists Find Hidden Defect That May Explain Why IBD Flares Keep Returning

Inflammatory bowel disease (IBD), a group of conditions that includes Crohn's disease and ulcerative colitis, causes chronic inflammation in the digestive tract, with abdominal pain, diarrhoea, fatigue and weight loss interrupted by unpredictable flare-ups. Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI), working with the Royal Melbourne Hospital, have found a hidden molecular defect that may explain why these flare-ups return even when a patient appears well. The findings were published in the journal Science.

The team found that intestinal cells stay primed to die even in patients with few or no symptoms, and that higher levels of this cell-death signalling were linked to a greater likelihood of relapse over more than two years of follow-up. Study co-author Dr Andre Samson said that even once a patient becomes symptom-free on treatment, there remains a likelihood of a future flare. Professor James Murphy, a WEHI deputy director and lab head, described it as a 'smouldering' defect that appears very early in the disease, before obvious signs of active inflammation.

IBD affects around 180,000 Australians, and modern treatments can bring many patients into remission, but the disease remains hard to diagnose and treat consistently. Unlike earlier work that relied mainly on mouse models, this study was based entirely on human tissue: researchers collected around 900 biopsies from 80 people with and without IBD and used them to grow organoids, lab-grown miniature intestinal tissue derived from each patient's own cells. Professor Edwin Hawkins, head of WEHI's Colonial Foundation Diagnostics Centre, said the large patient group and the use of human tissue were major strengths of the study, since mouse models often do not accurately reflect the human condition. The results challenge the idea that intestinal cell death is simply a consequence of inflammation, suggesting instead that it may be part of the disease process itself.

The findings do not yet provide a new diagnostic test or treatment. Study co-author and gastroenterologist Dr Aysha Al-Ani said they instead lay the groundwork for future work, including more refined ways of assessing a patient's outlook and potential new therapies.