Blood test predicts Crohn's disease years before symptoms emerge

A team at Sinai Health has identified a blood test that can spot Crohn's disease years before a person feels the first symptom—a finding that could reshape how the disease is managed, moving treatment from crisis response to early intervention.

The test works by measuring how a person's immune system reacts to flagellin, a protein that sits on the surface of certain gut bacteria. In people destined to develop Crohn's disease, this immune response shows up long before any digestive trouble begins. The research, led by Dr. Ken Croitoru at the Lunenfeld-Tanenbaum Research Institute, was published in Clinical Gastroenterology and Hepatology and reveals something fundamental: the immune system's attack on these bacteria may actually trigger the disease, rather than being a response to it.

Crohn's disease itself is a chronic inflammation of the digestive tract that brings persistent pain, digestive problems, and fatigue—conditions that wear down quality of life over years. The disease has become more common in recent decades. Among children, cases have doubled since 1995. Crohn's and Colitis Canada projects that by 2035, roughly 470,000 Canadians will be living with inflammatory bowel disease. Current treatments help some patients but cure none. "With all of the advanced biologic therapy we have today, patients' responses are partial at best," Croitoru said. "We haven't cured anybody yet, and we need to do better."

The discovery emerged from the GEM Project, a long-running study that has tracked more than 5,000 healthy first-degree relatives of Crohn's patients since 2008. The researchers collect genetic, biological, and environmental data to understand how the disease develops. So far, 130 of these initially healthy participants have gone on to develop Crohn's—a rare window into the disease's earliest stages, before symptoms arrive. Collaborators at the University of Alabama had previously developed a test to detect antibodies against flagellin from Lachnospiraceae bacteria, a type found in the gut. Croitoru and his colleague Dr. Sun-Ho Lee wanted to know whether these antibodies would also appear in healthy people at risk of developing the disease.

They followed 381 first-degree relatives of Crohn's patients. Of those, 77 eventually developed the disease. Among those 77, more than a third—28 individuals—had shown elevated antibody responses to flagellin in their earlier blood tests. The effect was strongest in siblings, suggesting that shared environment plays a role in triggering this immune response. The researchers also confirmed that this pre-disease immune reaction was linked to intestinal inflammation and a weakened gut barrier, both hallmarks of Crohn's disease. On average, the time between the blood test showing elevated antibodies and the person's actual diagnosis was about two and a half years.

The implications are significant. If doctors can identify people with this immune signature years before symptoms emerge, they gain time to intervene. Dr. Lee noted that the immune response targets a specific part of the flagellin protein, which opens a possibility: designing a vaccine aimed at flagellin to prevent the disease in high-risk individuals. "This raises the potential for designing a flagellin-directed vaccine in selected high-risk individuals for prevention of disease," Lee said. Further studies are underway to validate the approach and understand the mechanics more deeply. For now, the blood test offers something medicine rarely has—a chance to see disease coming and potentially stop it before it starts.