Researchers at Sinai Health have developed a groundbreaking blood test capable of predicting Crohn’s disease years before any symptoms manifest. This advance may lead to earlier diagnosis and even prevention of the chronic inflammatory condition affecting the gastrointestinal tract.
The innovative test evaluates the immune response to flagellin, a protein associated with gut bacteria. Elevated responses to this protein have been identified in individuals long before they develop Crohn’s disease. The research team, led by Dr. Ken Croitoru, a clinician scientist at the Lunenfeld-Tanenbaum Research Institute, included gastrointestinal medical resident Dr. Richard Wu and clinician scientist and gastroenterologist Dr. Sun-Ho Lee. Their findings were published in the journal Clinical Gastroenterology and Hepatology.
Significance of the Findings
The study highlights how the interaction between gut bacteria and immune system responses may play a crucial role in the onset of Crohn’s disease. This condition is characterized by persistent digestive symptoms, abdominal pain, and fatigue, significantly impacting individuals’ quality of life. Alarmingly, the incidence of Crohn’s disease among children has doubled since 1995, with projections indicating that approximately 470,000 Canadians will be living with inflammatory bowel disease (IBD) by 2035, according to Crohn’s and Colitis Canada.
Dr. Croitoru emphasized that the presence of flagellin antibodies prior to symptom onset suggests this immune reaction could be a trigger for the disease, rather than just a consequence. “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,” he stated.
Research Methodology and Results
This study is part of the Genetic, Environmental and Microbial (GEM) Project, a global initiative involving over 5,000 healthy first-degree relatives of Crohn’s patients. Since its inception in 2008, the project has gathered genetic, biological, and environmental data to deepen understanding of Crohn’s disease development. So far, 130 participants have developed the condition, allowing researchers to analyze the earliest stages of the disease.
Previous findings revealed that an inflammatory immune response targeting gut bacteria can emerge long before Crohn’s disease manifests. In healthy individuals, beneficial bacteria coexist peacefully in the gut, but in Crohn’s patients, the immune system mistakenly attacks these microbes. Collaborators at the University of Alabama, led by Dr. Charles Elson, previously established a test to detect antibodies against flagellin. They found that individuals with Crohn’s disease exhibit elevated antibody levels against flagellin from Lachnospiraceae bacteria.
Drs. Croitoru and Lee aimed to determine whether this immune response could also be present in healthy individuals at risk of developing Crohn’s disease. “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,” Dr. Croitoru explained.
The study analyzed 381 first-degree relatives of Crohn’s patients, with 77 ultimately developing the disease. Among these individuals, 28—over a third—had elevated antibody responses, particularly strong in siblings, underscoring the importance of shared environmental exposure.
The researchers confirmed that the pre-disease response to Lachnospiraceae flagellin correlated with intestinal inflammation and gut barrier dysfunction, both of which are characteristic of Crohn’s disease. The typical timeline from blood sample collection to diagnosis for these pre-disease individuals 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 the prevention of disease. Further validation and mechanistic studies are underway.”
This pioneering research represents a significant step forward in understanding Crohn’s disease, offering hope for improved predictive and preventive measures in the future.
