Hidden gut cell defect may explain why IBD flares keep returning
Australian researchers have found that intestinal cells in people with inflammatory bowel disease can carry a hidden, 'smoldering' molecular defect even during apparent remission, raising the risk of relapse. The discovery could pave the way for better prediction and more personalized treatment.
Scientists at WEHI, working with the Royal Melbourne Hospital, have identified a hidden molecular problem in intestinal cells that may leave them vulnerable to damage long before symptoms of inflammatory bowel disease (IBD) appear — and that can persist even when a patient's condition seems well controlled. The findings were published in the journal Science.
IBD, which includes Crohn's disease and ulcerative colitis, is a chronic condition affecting around 180,000 people in Australia. Patients can experience rectal bleeding, abdominal pain, diarrhea, fatigue and weight loss, with the disease typically cycling between periods of remission and sudden, sometimes severe flare-ups.
Cells primed to die
According to co-author Dr. Andre Samson, the team found that intestinal cells in patient samples appeared "primed to die," with the defect persisting even in patients who were essentially symptom-free. This challenges the assumption that cell death in IBD is merely a consequence of inflammation — the researchers instead suggest it may actively help drive the disease.
Professor James Murphy said the defect, described as a "smoldering" molecular problem, was already detectable during the earliest stages of disease activity, including in patients with only mild IBD — pointing to it as one of the first dominoes to fall in disease progression.
Built entirely on human tissue
The research relied on around 900 biopsies from 80 people with and without IBD, used to grow patient-derived organoids for direct study of human gut tissue rather than mouse models. Patients were tracked for more than two years, and those with stronger intestinal cell death signals were found to be more likely to relapse.
Co-author Dr. Aysha Al-Ani cautioned that the discovery won't immediately translate into a new diagnostic test or treatment, but said it lays groundwork for more sophisticated prognostic tools and treatments tailored to how an individual's disease behaves at the molecular level, with the aim of keeping patients in remission for longer.
