Sinai Health researchers have developed a blood test that can predict Crohn's disease years before symptoms appear. The study, led by Dr. Ken Croitoru at the Lunenfeld-Tanenbaum Research Institute and including Dr. Richard Wu and Dr. Sun-Ho Lee, found that the test measures immune response to flagellin, a protein present on gut bacteria. Elevated levels of this immune response were detected in individuals long before they developed Crohn's disease.
Drs. Croitoru and Lee are also affiliated with Mount Sinai Hospital's Centre for Inflammatory Bowel Disease, which is known internationally for its research in this field. Their findings were published in Clinical Gastroenterology and Hepatology.
Crohn's disease is a chronic inflammatory disorder affecting the gastrointestinal tract, causing persistent digestive problems, pain, and fatigue. The incidence among children has doubled since 1995 and continues to increase. According to Crohn's and Colitis Canada, it is estimated that about 470,000 Canadians will be living with inflammatory bowel disease by 2035.
Dr. Croitoru explained that the presence of antibodies against flagellin well before symptoms appear suggests the immune reaction may help trigger the onset of Crohn's disease rather than being a result of it. He stated: "With all of the advanced biologic therapy we have today, patients' responses are partial at best. We haven't cured anybody yet, and we need to do better."
This research is part of the Genetic, Environmental and Microbial (GEM) Project led by Dr. Croitoru since 2008, involving more than 5,000 healthy first-degree relatives of people with Crohn's disease worldwide. So far, 130 participants have developed the condition during follow-up.
Earlier work from collaborators at the University of Alabama led by Dr. Charles Elson had produced a test detecting antibodies against flagellin from Lachnospiraceae bacteria; individuals with Crohn's showed higher antibody levels against these proteins.
The new study tracked 381 first-degree relatives of patients with Crohn’s; 77 eventually developed the disease over time. Among them, more than one-third—28 people—had elevated antibody responses before diagnosis; siblings showed especially strong responses due to shared environmental factors previously identified by Dr. Croitoru’s group.
Researchers confirmed that pre-disease antibody responses correlated with intestinal inflammation and impaired gut barrier function—both hallmarks of Crohn’s disease—with an average time between blood sample collection and diagnosis being about two-and-a-half years.
Dr. Lee said: "Confirming our previous study immune response against bacterial flagellins show strong associations with future risk of Crohn's in healthy first-degree relatives." He added: "We found that this immune response is driven by a conserved domain of the flagellin protein. This raises the potential for designing a flagellin-directed vaccine in selected high-risk individuals for prevention of disease. Further validation and mechanistic studies are underway."
