A test that rapidly detects signs of inflammatory bowel disease (IBD) in stool samples could improve future diagnosis and monitoring of the condition, a study suggests.
Scientists have developed a tool to measure the activity of a molecule linked to gut inflammation within faecal samples.
The optical tool, known as a luminescent reporter, lights up when it detects the molecule, with higher readouts indicating increased activity and inflammation.
The new technique could boost the accuracy of stool sample tests for IBD, reducing the need for invasive, expensive procedures, experts say.
Gut inflammation
IBD is a chronic illness where the body’s immune system mistakenly attacks the digestive tract, leading to long-lasting inflammation. Diagnosis and monitoring of the condition often rely on colonoscopies, where a small camera is used to examine the gut.
Current IBD stool tests measure general markers of inflammation, such as the protein calprotectin, so a positive result requires further investigation to confirm the source.
University of Edinburgh researchers studied gut tissue from IBD patients and identified high levels of an enzyme – a molecule that speeds up chemical reactions in cells – called granzyme A (GzmA) in inflamed gut tissue compared with non-inflamed tissues.
Microscopy images of colon tissue samples from IBD patients under remission (left) and with active disease (right). Granzyme A, indicated by green fluorescence, is elevated in the intestinal tract of IBD patients with active disease. Credit: Emily Thompson.
Enzyme activity
GzmA is released by T cells – a type of white blood cell – which usually protect the body by finding and fighting infections or abnormal cells. In IBD, T cells mistakenly see the gut as a threat and become overactive, which can lead to tissue damage and inflammation.
The research team developed a luminescent reporter to measure the activity of GzmA in stool samples. The reporter tool was tested on 150 samples from both IBD and healthy patients.
Combining the new reporting tool with the current common testing of faecal calprotectin levels was more successful in identifying IBD in patients than using faecal calprotectin scores alone.
Researchers say the ability to identify gut-specific inflammation is a step forward for IBD diagnosis, but caution further research is needed before it can be used in a clinical setting.
Spin-out company
The tool will form part of the assets of a new company in the process of spinning out of the University of Edinburgh, called IDXSense, supported by Edinburgh Innovations, the University’s commercialisation service.
The technique could also support the development of personalised IBD treatments in the future, with the ability to rapidly and accurately monitor gut inflammation levels in response to different therapies, experts say.
The speed and sensitivity of our optical tool has the potential to accelerate future studies into the roles of the immune system in IBD, as well as improving the pathway to diagnosis. In the future, these optical tools could also be used to help tailor treatments for IBD patients.
Professor Marc Vendrell
Study lead from the Institute for Regeneration and Repair
The IDXSense pre-spinout team, led by Marc Vendrell, is designing, developing and manufacturing novel, non-invasive, in-vitro diagnostic devices for IBD, and we are actively looking for partners to help us transform health outcomes in this area of unmet medical need.
Lizzie Withington
Director of Venture Creation at Edinburgh Innovations
This important study is a wonderful example of fundamental chemists working closely with doctors who understand how the gut works. We need better tests that can tell us about the mechanisms rather than simply measuring inflammation to help us treat patients better.
Professor Gwo-Tzer Ho
Co-author and IBD expert, University of Glasgow
The research team included scientists from the Universities of Edinburgh, Glasgow, Groningen and Tel Aviv. The study was funded by the European Research Coucil (ERC), the European Innovation Council (EIC), the Medical Research Council, Marie Sklodowska-Curie Awards and Leona M. and Harry B. Helmsley Charitable Trust.
