Researchers at Sinai Health have developed a groundbreaking blood test capable of predicting Crohn’s disease years before symptoms manifest, potentially paving the way for early diagnosis and prevention strategies. This innovative test measures an individual’s immune response to flagellin, a protein found on gut bacteria, which is elevated in susceptible individuals long before the onset of Crohn’s Disease.
The study, led by Dr. Ken Croitoru, a clinician scientist at the Lunenfeld-Tanenbaum Research Institute, part of Sinai Health, included contributions from gastrointestinal medical resident Dr. Richard Wu and clinician scientist Dr. Sun-Ho Lee. Their findings, published in Clinical Gastroenterology and Hepatology, underscore the critical role of the gut’s bacterial and immune system interactions in the development of Crohn’s Disease.
Understanding Crohn’s Disease
Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract, causing persistent digestive symptoms, pain, and fatigue, which significantly impact quality of life. Since 1995, the incidence of Crohn’s among children has doubled, and rates continue to escalate. According to Crohn’s and Colitis Canada, a non-profit organization dedicated to curing inflammatory bowel disease (IBD), approximately 470,000 Canadians are projected to be living with IBD by 2035.
The presence of flagellin antibodies long before any symptoms appear suggests that this immune reaction may initiate the disease rather than result from it. Dr. Croitoru emphasizes that understanding this early process could lead to novel approaches for predicting, preventing, and treating Crohn’s Disease.
“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,” said Dr. Croitoru, who holds the Canada Research Chair in Inflammatory Bowel Diseases.
The GEM Project’s Role
This research is part of the Genetic, Environmental, and Microbial (GEM) Project, a global cohort study involving more than 5,000 healthy first-degree relatives of individuals with Crohn’s disease, led by Dr. Croitoru. Since 2008, the project has amassed genetic, biological, and environmental data to elucidate the disease’s development. To date, 130 participants have developed Crohn’s, offering researchers a rare opportunity to study the earliest pre-disease stages.
Previously, the team discovered that an inflammatory immune response targeting gut bacteria can appear long before Crohn’s disease develops. In healthy individuals, bacteria coexist peacefully in the gut, playing an essential role in maintaining digestive health. However, in Crohn’s disease, the immune system mounts an abnormal response against these normally beneficial microbes.
Key Findings and Future Implications
Collaborators at the University of Alabama, led by Dr. Charles Elson, had previously developed a test to detect antibodies against flagellin, demonstrating that individuals with Crohn’s have elevated antibody levels targeting flagellin from Lachnospiraceae bacteria. Drs. Croitoru and Lee sought to determine whether this immune response could also be detected in healthy individuals at risk of developing the disease.
“We wanted to know: do people who are at risk, who are healthy now, have these antibodies against flagellin?” said Dr. Croitoru. “We looked, we measured, and yes indeed, at least some of them did.”
This study followed 381 first-degree relatives of Crohn’s patients, 77 of whom developed the disease. Among them, 28 individuals—more than a third—had elevated antibody responses. The responses were strongest in siblings, underscoring the role of shared environmental exposure.
The researchers confirmed that this pre-disease response to the Lachnospiraceae flagellin was associated with intestinal inflammation and gut barrier dysfunction, both characteristic of Crohn’s disease. The typical timeline from blood sample collection to diagnosis was nearly two and a half years.
“Confirming our previous study, immune responses against bacterial flagellins show strong associations with future risk of Crohn’s in healthy first-degree relatives,” said Dr. Lee. “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.”
Looking Ahead
The potential to predict and possibly prevent Crohn’s Disease through early detection represents a significant advancement in the field of gastroenterology. As research continues, the development of targeted vaccines and therapies could transform the management of this chronic condition, offering hope to those at risk and improving the quality of life for countless individuals.
As the GEM Project progresses, further insights into the genetic, environmental, and microbial factors contributing to Crohn’s Disease will likely emerge, providing a more comprehensive understanding of this complex illness and informing future treatment strategies.
