Smouldering disease activity linked to IBD relapse, even in remission

Crohn’s & Colitis Australia-backed research, published in Science, finds molecular ‘warning signs’ can persist despite apparent IBD remission, with higher levels linked to subsequent relapse.

SYDNEY, 26 AUGUST 2026: People with inflammatory bowel disease (IBD) can feel well and have a bowel that appears healed, while abnormal disease processes continue beneath the surface, according to new Australian research published in Science. The study, supported by Crohn’s & Colitis Australia (CCA), uncovered persistent abnormal cell-death signalling in the intestinal lining of people with IBD, including patients whose disease was well controlled and in tissue with little or no apparent inflammation.

Importantly, the team followed patients for more than two years and found that those with higher levels of this abnormal cell-death signalling were more likely to subsequently experience a clinical relapse. The findings raise the possibility that molecular changes in the intestinal lining could one day help identify patients whose disease remains biologically active despite apparent remission — and reveal new treatment targets aimed at achieving deeper and more durable remission.

The research was a major collaboration between clinicians and scientists at The Royal Melbourne Hospital (RMH) and WEHI, bringing together a deeply characterised IBD patient cohort and longitudinal clinical data with expertise in cell-death biology, spatial molecular analysis and patient-derived intestinal organoids. The multidisciplinary team included Associate Professor Britt Christensen and Dr Aysha Al-Ani at RMH, together with Professor James Murphy, Professor James Vince, Dr Andre Samson, Professor Edwin Hawkins, Dr Jiyi Pang and a broader team of researchers from WEHI and collaborating institutions.

Dr Al-Ani, whose PhD was supported by a Crohn’s & Colitis Australia top-up scholarship, undertook the work under the supervision of A/Prof Christensen, Professor Murphy and Dr Samson. IBD, which includes Crohn’s disease and ulcerative colitis, is a lifelong condition in which periods of remission can be interrupted by unpredictable disease flares. Modern treatments can achieve excellent control of inflammation, yet some patients who feel well, have reassuring tests and appear to have achieved healing will subsequently relapse.

“One of the frustrations in treating IBD is that a patient can be feeling well, their tests can look reassuring and their bowel can appear healed, but we still can’t be certain that the disease is truly switched off,” A/Prof Christensen said.

“What surprised us was that although many of the patients in our study had well-controlled disease and the majority were in endoscopic remission, we could still see increased cell-death signalling in the intestinal lining. It suggests there may be disease still smouldering beneath the surface.

“That finding led us to ask whether these signals had any bearing on what happened to patients later. When we looked at their subsequent clinical course, patients with higher levels of this signalling were more likely to relapse.

“That opens up two really interesting possibilities. The first is whether we could eventually use these molecular changes to identify patients who are still at risk of a flare despite appearing to be in remission. The second is whether these pathways themselves could become treatment targets, allowing us to treat the disease that remains beneath apparent remission and help patients stay well for longer.”

A ‘smouldering’ abnormality beneath remission

A major strength of the study was that it was built around human tissue and detailed clinical data. The team studied more than 900 intestinal biopsies from 80 people with and without IBD and combined these samples with longitudinal clinical outcomes, spatial molecular analysis and patient-derived intestinal organoids.

The researchers found evidence of a persistent, or ‘smouldering’, abnormality in the way intestinal cells respond to inflammatory signals. Even in tissue without obvious active inflammation, cells forming the protective lining of the gut showed abnormal cell-death signalling.

Using advanced molecular techniques and patient-derived organoids, the researchers investigated how these abnormal signals develop. Their experiments showed how inflammatory signals can drive abnormal cell-death pathways, damaging both mature cells that form the gut barrier and the intestinal stem cells responsible for continually repairing and regenerating it.

“The ethos behind IBD therapy is to reduce the frequency and severity of flares, halt disease progression and improve patients’ lives,” Dr Al-Ani said.

“More sensitive molecular detection may help us keep patients in deep remission for longer and introduce new treatments.”

What could this mean for people living with IBD?

The findings do not provide an immediate new diagnostic test or treatment. Clinicians currently use a combination of symptoms, blood and stool biomarkers, endoscopy, histology and imaging to determine whether IBD is adequately controlled. The new research suggests there may be an additional biological layer beneath those conventional measures. If these molecular signals are validated in larger prospective studies, they could potentially help distinguish patients who have achieved a deeper and more durable remission from those whose disease remains biologically active despite appearing well.

This could ultimately allow monitoring and treatment to be more precisely tailored to an individual patient’s risk — for example, identifying people who may benefit from closer follow-up or a different treatment strategy despite appearing to be in remission by conventional measures.

The findings also raise the possibility that abnormal cell-death pathways could themselves become future treatment targets. Current IBD therapies can be highly effective at suppressing inflammation, but the new research suggests abnormal cell-death signalling within the intestinal lining may persist despite apparent disease control.

Future research will determine whether interrupting these pathways can protect intestinal epithelial and stem cells and help achieve a deeper and more durable state of remission.

Crohn’s & Colitis Australia CEO Leanne Raven said the findings addressed an important source of uncertainty for people living with IBD.

“For people living with IBD, being told you are in remission should bring reassurance, yet many people still live with the uncertainty of when the next flare might come,” Ms Raven said.

“Research like this helps us understand what may be happening beneath the surface, even when someone appears to be well.

“The hope is that research of this kind will ultimately give people greater confidence that remission can last — by helping clinicians identify those who remain at risk and opening the door to treatments that could keep disease under control for longer.”

Supporting the next generation of IBD researchers

CCA supported Dr Al-Ani during her PhD through a top-up scholarship, helping her develop as a clinician-researcher while undertaking work that contributed to the study.

A/Prof Christensen, who supervised Dr Al-Ani’s PhD, said supporting young clinicians to become researchers was particularly important for the future of IBD care.

“Aysha’s PhD is a great example of what can happen when we give young clinicians the opportunity to ask research questions that come directly from caring for patients,” A/Prof Christensen said.

“CCA’s support of emerging IBD researchers matters. It helps us develop people who can move between the clinic and the laboratory and, ultimately, bring what we learn through research back to our patients.”

For people living with IBD, the long-term goal is not simply to treat a flare when it occurs, but to understand why disease returns and, one day, identify and treat the processes driving it early enough to prevent the next flare.

ENDS

Notes to Editors

• The study, ‘A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease’, is published in Science.
• The research was a collaboration between the Royal Melbourne Hospital and WEHI and included around 900 intestinal biopsies from 80 people with and without IBD, alongside patient-derived intestinal organoid research.
• The research was supported by the Kenneth Rainin Foundation, National Health and Medical Research Council of Australia (NHMRC), Australian Research Council, Stafford Fox Medical Research Foundation and Victorian State Government. Dr Aysha Al-Ani’s PhD was supported by a Crohn’s & Colitis Australia top-up scholarship.
• Dr Aysha Al-Ani’s PhD was supported by a Crohn’s & Colitis Australia top-up scholarship.
• Crohn’s & Colitis Australia is a national organisation supporting people living with Crohn’s disease and ulcerative colitis through support, education, advocacy and research funding.

Media contact: Sophie Muir | Maven PR | [email protected] | +61 (0)400 111 390

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