Blood test predicts Crohn's disease years before symptoms emerge

A team at Sinai Health has identified a blood test that can detect Crohn's disease years before a person experiences any symptoms, potentially reshaping how the condition is diagnosed and treated. The test measures the body's immune response to flagellin, a protein found on certain gut bacteria. Researchers led by Dr. Ken Croitoru discovered that people destined to develop Crohn's show elevated antibody responses to this protein long before the disease manifests—suggesting that the immune system's attack on these bacteria may actually trigger the disease rather than result from it.

Crohn's disease is a chronic inflammatory condition that damages the digestive tract, causing persistent pain, digestive problems, and fatigue that can severely limit daily life. The disease has become increasingly common, particularly among children; incidence rates among young people have doubled since 1995. Crohn's and Colitis Canada projects that roughly 470,000 Canadians will be living with inflammatory bowel disease by 2035. Current treatments, while advanced, offer only partial relief. "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," Croitoru said.

The research emerged from the Genetic, Environmental and Microbial Project, a global study that has tracked more than 5,000 healthy first-degree relatives of people with Crohn's disease since 2008. By collecting genetic, biological, and environmental data over nearly two decades, researchers created a rare window into the earliest stages of disease development. To date, 130 participants in the cohort have gone on to develop Crohn's, providing researchers with the opportunity to study what happens in the body before symptoms ever appear.

In the current study, researchers followed 381 first-degree relatives of Crohn's patients. Among them, 77 eventually developed the disease. Of those 77, more than a third—28 individuals—had shown elevated antibody responses to flagellin in their blood samples taken years earlier. The immune response was particularly strong in siblings, suggesting that shared household environment plays a significant role in who develops these early warning signs. The typical interval between the blood test and diagnosis was approximately two and a half years.

The findings, published in Clinical Gastroenterology and Hepatology, reveal something fundamental about how Crohn's develops. In healthy people, gut bacteria live in balance with the immune system, contributing to digestive health. In Crohn's disease, the immune system launches an abnormal attack against these normally beneficial microbes. The new research shows this aberrant immune response can be detected in the blood long before inflammation damages the intestines. Researchers confirmed that the pre-disease immune response was associated with intestinal inflammation and compromised gut barrier function—both hallmarks of Crohn's disease.

Dr. Sun-Ho Lee, who worked on the study alongside Croitoru and resident Dr. Richard Wu, noted that the immune response targets a specific, conserved region of the flagellin protein. This precision opens a concrete possibility: designing a vaccine that trains the immune system to tolerate flagellin, potentially preventing disease in people identified as high-risk. "Confirming our previous study immune response against bacterial flagellins show strong associations with future risk of Crohn's in healthy first-degree relatives," Lee said. "This raises the potential for designing a flagellin-directed vaccine in selected high-risk individuals for prevention of disease."

The implications extend beyond diagnosis. If researchers can identify who will develop Crohn's years in advance, and if a preventive vaccine proves effective, the disease's trajectory could shift fundamentally. Rather than waiting for symptoms to emerge and then managing a chronic condition, clinicians could intervene before inflammation takes hold. The team is now pursuing further validation studies and investigating the mechanisms that drive this immune response, work that could reshape treatment strategies for one of the most burdensome gastrointestinal diseases.