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Researchers at the Icahn School of Medicine at Mount Sinai have identified immune system changes that can be detected up to 10 years before inflammatory bowel disease (IBD) develops, offering new insight into how the disease begins.
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Published July 21 in Gut, the study is one of the most comprehensive investigations to date of the preclinical phase of IBD. Using antibody profiling technology, researchers analyzed nearly 2,000 blood samples collected over about a decade from people who later developed Crohn's disease or ulcerative colitis.
They identified unique antibody signatures against viruses and bacteria—particularly Epstein-Barr virus and bacterial flagellins—that were present years before diagnosis, suggesting that abnormal immune activity begins long before the disease becomes clinically apparent.
Tracking immune changes over time
"IBD does not develop overnight," said Saurabh Mehandru, M.D., corresponding author of the study and professor of medicine (gastroenterology) at the Icahn School of Medicine at Mount Sinai. "Our findings show that the immune system is already changing years before patients experience their first symptoms. By understanding these early immune changes, we hope to uncover the biological events that trigger disease and ultimately develop strategies to identify, and one day prevent, IBD before it starts."
Researchers profiled antibody responses against 357,000 viral, bacterial and other antigens in blood samples collected approximately 10 years, four years and two years before diagnosis, as well as shortly after diagnosis. The study included 200 people who later developed Crohn's disease, 200 people who developed ulcerative colitis and 100 healthy individuals. Antibody responses evolved over time and differed significantly between people who developed IBD and those who remained healthy. Many of the strongest signals were already detectable at the earliest time point, approximately 10 years before diagnosis.
Among the most striking findings were elevated antibody responses against Epstein-Barr virus and bacterial flagellins in people who later developed Crohn's disease. These immune signatures remained detectable years before diagnosis and support growing evidence that interactions between infections, the gut microbiome and the immune system may contribute to the earliest stages of IBD. The findings also support the theory of molecular mimicry, in which immune responses to viruses or bacteria may inadvertently target the body's own tissues.
"This study allowed us to watch the immune system evolve over an entire decade before disease was diagnosed," said Arno R. Bourgonje, M.D., Ph.D., first author of the study and a postdoctoral fellow in gastroenterology at the Icahn School of Medicine at Mount Sinai. "By mapping antibody responses over time, we identified distinct patterns that separate people who later develop IBD from those who remain healthy. These findings provide an important framework for understanding the earliest stages of disease development."
Toward earlier risk detection
While additional research is needed before these antibody signatures can be used clinically, the findings could eventually help identify people at increased risk for IBD, particularly relatives of patients with the disease, and guide future prevention strategies.
"For years, we've known that inflammatory bowel disease has a long silent phase before symptoms emerge, but we have had limited insight into what is happening during that period," said Jean-Frédéric Colombel, M.D., co-corresponding author of the study and director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai. "This work provides one of the clearest pictures yet of the immune changes that precede IBD and moves the field closer to earlier diagnosis and, ultimately, disease prevention." Colombel is also a professor of medicine (gastroenterology) at Mount Sinai.
The study was conducted by researchers at the Icahn School of Medicine at Mount Sinai in collaboration with the Medical University of Vienna in Austria. The investigators will continue studying the biology of the preclinical phase of IBD to better understand disease initiation and develop strategies to identify and prevent disease before symptoms arise.
More information: Arno R Bourgonje et al, Deciphering the prodrome of inflammatory bowel disease up to 10 years before disease onset by massively parallel serology, Gut (2026). DOI: 10.1136/gutjnl-2025-337762
Provided by The Mount Sinai Hospital
This story was originally published on Medical Xpress.
