A blood test could reveal Crohn’s disease years before symptoms

The blood test focuses on how the immune system reacts to flagellin, a protein found on certain gut bacteria. According to a research team led by Dr. Ken Croitoru, a clinician scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, people who later develop Crohn's disease often show higher immune responses to this protein long in advance. The study team also included gastrointestinal medical resident Dr. Richard Wu and clinician scientist and staff gastroenterologist Dr. Sun-Ho Lee.

Drs. Croitoru and Lee are also members of Mount Sinai Hospital's Centre for Inflammatory Bowel Disease (IBD), an internationally recognized center dedicated to inflammatory bowel disease research.

The findings were published in Clinical Gastroenterology and Hepatology and emphasize how interactions between gut bacteria and the immune system play a crucial role in the early development of Crohn's disease.

A Disease on the Rise

Crohn's disease is a chronic inflammatory disorder of the digestive tract that can lead to ongoing digestive problems, pain, and fatigue. These symptoms often have a major impact on daily life. Since 1995, rates of Crohn's disease in children have doubled, and overall cases continue to increase. Crohn's and Colitis Canada, a non profit organization focused on curing inflammatory bowel disease, estimates that about 470,000 Canadians will be living with IBD by 2035.

Why Early Antibodies Matter

Detecting antibodies to flagellin years before symptoms appear suggests that this immune response may help trigger the disease rather than simply result from it, Dr. Croitoru said. He believes that understanding these early immune changes could lead to new ways to predict who is at risk, prevent the disease from developing, and improve treatment.

"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 hold Canada Research Chair in Inflammatory Bowel Diseases.

Tracking Risk Through the GEM Project

The study is part of the Genetic, Environmental and Microbial (GEM) Project, a large international effort led by Dr. Croitoru. The project follows more than 5,000 healthy first degree relatives of people with Crohn's disease. Since 2008, researchers have collected genetic, biological, and environmental information to better understand how the disease begins. So far, 130 participants have gone on to develop Crohn's disease, allowing scientists to examine the condition before symptoms emerge.

Earlier work from the team showed that an inflammatory immune response aimed at gut bacteria can appear well before Crohn's disease is diagnosed. In healthy individuals, gut bacteria normally live in balance with the body and support digestion. In people with Crohn's disease, the immune system appears to react abnormally to microbes that are usually beneficial.

Building on Earlier Discoveries

Previous research by collaborators at the University of Alabama, led by Dr. Charles Elson, resulted in a test that detects antibodies against flagellin. That work showed that people with Crohn's disease often have higher antibody levels directed at flagellin from Lachnospiraceae bacteria.

Drs. Croitoru and Lee then asked whether the same immune response could be found in healthy people who were at increased 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?" said Dr. Croitoru. "We looked, we measured, and yes indeed, at least some of them did."

Study Results and What Comes Next

The study followed 381 first degree relatives of people with Crohn's disease. During the study period, 77 participants developed the condition. Among them, 28 individuals had elevated antibody levels, accounting for more than a third of those who became ill. The strongest immune responses were seen in siblings, underscoring the importance of shared environmental exposure, as shown previously by Dr. Croitoru.

Researchers also confirmed that this early immune response to Lachnospiraceae flagellin was linked to intestinal inflammation and problems with the gut barrier, both key features of Crohn's disease. On average, participants were diagnosed nearly two and a half years after their blood samples were collected.

"Confirming our previous study immune response 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."