Test can detect Crohn’s disease years before symptoms show

The discovery opens the door to early diagnosis and potential prevention of the chronic form of inflammatory bowel disease (IBD), say Canadian scientists.

The new test measures a person’s immune response to flagellin, a protein found on gut bacteria.

The research team explained that the response is elevated in people long before they develop Crohn’s.

They say their findings, published in the journal Clinical Gastroenterology and Hepatology, highlight the "interplay" between the gut’s bacteria and immune system responses as a key step in developing Crohn’s.

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that causes persistent digestive symptoms, pain and tiredness, significantly affecting quality of life.

Its incidence among children has doubled since 1995, according to official figures.

Research leader Dr. Ken Croitoru says the presence of flagellin antibodies long before any symptoms appear suggests that the immune reaction may contribute to triggering the onset of the disease, rather than being a consequence of it.

He believes that a better understanding of the early process could open the door to new ways for predicting, preventing and treating the disease.

Dr. Croitoru said: “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.”

The research is part of the Genetic, Environmental and Microbial (GEM) Project, a group of more than 5,000 healthy first-degree relatives of people with Crohn’s disease around the world.

Since 2008, the project has collected genetic, biological and environmental data to better understand how the disease develops.

To date, 130 participants have developed Crohn’s, giving researchers a rare opportunity to study the earliest pre-disease stages.

Previously, the team discovered that long before Crohn’s disease develops, an inflammatory immune response targeting gut bacteria can appear.

In healthy people, bacteria coexist peacefully in the gut and play an essential role in maintaining digestive health.

But in Crohn’s Disease the immune system appears to mount an abnormal response against normally beneficial microbes.

American scientists had previously developed a test to detect antibodies against flagellin and showed that people with Crohn’s have elevated antibody levels targeting flagellin from Lachnospiraceae bacteria.

The Canadian team wanted to determine whether the immune response could also be detected in healthy people who are at risk of developing the disease.

Dr. Croitoru, of the Lunenfeld-Tanenbaum Research Institute in Toronto, said: “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.”

This study followed 381 first-degree relatives of Crohn’s patients, 77 of whom went on to develop the disease.

Among them, 28 – more than a third – had elevated antibody responses.

The responses were strongest in siblings, highlighting the role of shared environmental exposure, as previously shown by Dr. Croitoru.

The researchers also confirmed that this pre-disease response to the Lachnospiraceae flagellin was associated with intestinal inflammation and gut barrier dysfunction, both of which are characteristics of Crohn’s disease.

The typical timeline from blood sample collection to the pre-disease individuals being diagnosed with Crohn’s was nearly two-and-a-half years, according to the findings.

Research team member Dr. Sun-Ho Lee said: “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."

Gastroenterologist Dr. Lee added: "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.”