Researchers have developed a blood test that detects an elevated immune response to gut bacteria, signaling the risk of Crohn's disease years before symptoms appear. The test, focusing on antibodies to flagellin from Lachnospiraceae bacteria, was identified through a study of healthy relatives of Crohn's patients. This discovery could enable earlier interventions to prevent the condition's progression.
A team at Sinai Health, led by clinician scientist Dr. Ken Croitoru, has pinpointed a blood test capable of revealing Crohn's disease risk long before clinical symptoms emerge. The test measures immune responses to flagellin, a protein on certain gut bacteria, particularly from Lachnospiraceae. By examining blood samples from healthy first-degree relatives of Crohn's patients, the researchers found that elevated antibody levels to this protein predicted disease development in over a third of cases that later occurred.
The findings stem from the Genetic, Environmental and Microbial (GEM) Project, an international initiative directed by Dr. Croitoru that has tracked more than 5,000 healthy first-degree relatives since 2008. Among 381 participants in this specific study, 77 developed Crohn's disease, with 28 showing high flagellin antibody levels beforehand. Siblings exhibited the strongest responses, highlighting shared environmental factors. On average, diagnoses followed blood collection by nearly 2.5 years.
Crohn's disease, a chronic inflammatory disorder of the digestive tract, causes ongoing issues like pain, fatigue, and digestive problems. Rates in children have doubled since 1995, and Crohn's and Colitis Canada projects 470,000 Canadians living with inflammatory bowel disease by 2035. The study links early immune reactions to gut barrier issues and inflammation, key hallmarks of the disease.
"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 noted. He added, "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."
Dr. Sun-Ho Lee, a co-author, emphasized the implications: "Confirming our previous study immune response against bacterial flagellins show strong associations with future risk of Crohn's in healthy first-degree relatives. 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."
The research builds on prior work by collaborators at the University of Alabama, led by Dr. Charles Elson, and was published in Clinical Gastroenterology and Hepatology.
