A blood test developed by researchers at Sinai Health could revolutionize the early diagnosis and prevention of Crohn’s disease. This groundbreaking test measures the immune response to flagellin, a protein present in gut bacteria, potentially allowing detection of the disease years before any symptoms manifest. A team led by Dr. Ken Croitoru, a clinician scientist at the Lunenfeld-Tanenbaum Research Institute, found elevated responses to this protein in individuals at risk of developing Crohn’s.
The research, which also involved Dr. Richard Wu and Dr. Sun-Ho Lee, has been published in the journal Clinical Gastroenterology and Hepatology. Their findings underscore the connection between gut bacteria and immune system responses as a pivotal factor in the onset of Crohn’s disease. This condition is characterized by chronic inflammation of the gastrointestinal tract, leading to persistent digestive issues, pain, and fatigue, ultimately affecting the quality of life.
The incidence of Crohn’s disease, particularly among children, has seen alarming increases, having doubled since 1995. By 2035, Crohn’s and Colitis Canada estimates that approximately 470,000 Canadians will be living with inflammatory bowel disease (IBD).
Dr. Croitoru posits that the presence of flagellin antibodies long before symptom onset may play a role in triggering the disease rather than simply being a reaction to it. He states, “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 study is part of the Genetic, Environmental and Microbial (GEM) Project, a comprehensive initiative that has been tracking over 5,000 healthy first-degree relatives of Crohn’s patients since 2008. The project collects genetic, biological, and environmental data to deepen the understanding of how Crohn’s disease develops. As of now, 130 participants have been diagnosed with Crohn’s, providing a unique opportunity for researchers to investigate the early stages of the disease.
Previous research by the team indicated that even before Crohn’s manifests, there can be an inflammatory immune response targeting gut bacteria. In healthy individuals, these bacteria coexist without issue, supporting digestive health. In contrast, Crohn’s disease triggers an atypical immune response against these generally beneficial microbes.
Collaborators at the University of Alabama, led by Dr. Charles Elson, previously developed a test to detect antibodies against flagellin. They found that individuals diagnosed with Crohn’s had significantly elevated antibody levels directed at flagellin from Lachnospiraceae bacteria. Dr. Croitoru and Dr. Lee sought to determine if this immune response could also be detected in at-risk but healthy individuals.
Dr. Croitoru noted, “We wanted to know: do people who are at risk, who are healthy now, have these antibodies against flagellin? We looked, we measured, and yes indeed, at least some of them did.”
The study monitored 381 first-degree relatives of Crohn’s patients, with 77 eventually developing the disease. Among these, over a third, specifically 28 individuals, exhibited elevated antibody responses. These responses were most pronounced in siblings, reinforcing the impact of shared environmental factors.
The research also confirmed that this pre-disease immune response to flagellin was associated with intestinal inflammation and gut barrier dysfunction, both hallmarks of Crohn’s disease. The average time from blood sample collection to diagnosis of Crohn’s was nearly two and a half years.
Dr. Lee emphasized the findings, stating, “Confirming our previous study, immune response against bacterial flagellins shows strong associations with future risk of Crohn’s in healthy first-degree relatives.” He added that this immune response is driven by a conserved domain of the flagellin protein, which opens the door for developing a flagellin-directed vaccine aimed at high-risk individuals for disease prevention. Further verification and mechanistic studies are currently underway.
The implications of this research could significantly change the landscape of Crohn’s disease management, highlighting the importance of early detection and intervention.
