Research led by Mount Sinai Hospital in Toronto shows antibodies against flagellin, the main protein that makes up the long tail on many gut bacteria, can be found in the blood of a significant proportion of at risk people who go on to develop Crohn’s disease.
The antibody response observed by the researchers was mainly directed at a small section of the flagellin protein, known as the hinge region, from normal gut bacteria and could be detected one to five years before diagnosis in those affected.
Crohn’s disease is an autoimmune disease affecting the digestive tract that can cause pain and serious complications, affecting almost one million people in the U.S. Earlier diagnosis could enable closer follow up and quick treatment to limit gut damage and complications.
“Elevated antimicrobial antibodies have been reported up to six years before diagnosis of Crohn’s disease, but the specific antibody response is unclear,” write the investigators in Clinical Gastroenterology and Hepatology.
In this study, the team included data from just under 400 close relatives of people with the inflammatory bowel disease, 77 who went on to develop Crohn’s and 304 who did not who acted as controls (matched for age, sex, duration of follow up and location). The researchers measured immune response to bacteria from blood samples taken one to four years before the group who developed the disease were diagnosed.
They measured antimicrobial antibodies on a microarray, then used a targeted bead based test for specific flagellin peptides, alongside testing for gut inflammation (fecal calprotectin and C reactive protein) and gut permeability.
People who later developed Crohn’s disease already showed more silent inflammation and gut barrier damage at baseline than relatives who stayed healthy. They had high levels of 28 of 49 antibodies, including 19 immunoglobulin (ig)G responses. Most of these were to Lachnospiraceae flagellins that were linked to roughly double the odds of future Crohn’s disease.
“We wanted to know: do people who are at risk, who are healthy now, have these antibodies against flagellin?” said co-lead author Ken Croitoru, MD, a clinician scientist at the Lunenfeld-Tanenbaum Research Institute, part of Sinai Health, in a press statement. “We looked, we measured, and yes indeed, at least some of them did.”
The results show a specific igG response to a conserved flagellin hinge peptide appears years before Crohn’s diagnosis in high risk relatives and is not simply a reflection of existing inflammation or a leaky gut.
The researchers say this antibody pattern could become a preclinical biomarker to identify high risk individuals and might point to new preventive or immune-based treatment strategies, but emphasize it needs confirmation and validation in other groups of people at risk for Crohn’s disease first.
