A new study led by researchers at Mount Sinai Health System has identified distinct biological signatures in patients with mild Crohn's disease, offering a potential pathway toward more personalized and less aggressive treatment strategies.
Published in Gastroenterology , the research is the first of its kind to use multi-omics data to study the biology of mild Crohn's disease, a condition that affects nearly one in four patients but is often overlooked, as most Crohn's disease research focuses on moderate-to-severe disease. Multi-omics is the combined study of different types of biological data (such as genes, proteins, and metabolites) to better understand how the body works and how diseases develop.
"These findings provide us with a new understanding of a large, overlooked group of patients," said Ryan C. Ungaro, MD, MS, Associate Professor, Medicine (Gastroenterology), Icahn School of Medicine at Mount Sinai, and senior author of this study. "Our research shows that mild Crohn's disease is not just a milder version of severe disease—it's biologically distinct."
Using data from two well-characterized patient cohorts—the Mount Sinai Crohn's and Colitis Registry observational cohort and the Ocean State Crohn's and Colitis Area Registry—first authors Arno Bourgonje, MD, PhD, and Susanne Ibing, PhD, postdoctoral fellows in gastroenterology at the Icahn School of Medicine, and the team discovered that patients with mild Crohn's disease exhibited a reduced immune response and altered sphingolipid metabolism—a cellular process linked to immune regulation. These molecular markers form a kind of biological fingerprint associated with lower risk of disease progression. These markers also distinguish mild disease from more aggressive forms.
Shortly after diagnosis, many Crohn's patients are prescribed advanced therapies that are aggressive, often costly, and lifelong treatments with potentially severe side effects (though rare). In a distinct subset of these patients, their symptoms never progress and they never need these advanced therapies. However, it is not yet well understood which patients will progress to more severe forms of the disease, and therefore will benefit from the advanced treatments. This study marks a major step toward navigating these nuances and providing precision medicine in inflammatory bowel disease (IBD), matching treatment intensity to the biology of the disease.
"We hope to develop tools that help physicians predict which patients are likely to have a mild, stable disease course," said Jean-Frédéric Colombel, MD, Director, Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, Icahn School of Medicine at Mount Sinai, and co-author on this paper. "That way, we can avoid unnecessary medications, reduce side effects, and lower costs for patients and the health care system. The findings in this paper could help change the outlook for patients with mild Crohn's disease." Dr. Colombel is also a Professor of Medicine (Gastroenterology).
The findings may support future use of biomarkers to identify patients who could safely delay or avoid biologic therapies. For patients, personalized care could mean fewer side effects, less time on medication, and lower treatment costs—especially for those with milder disease.
Looking ahead, researchers plan to validate these biomarkers in larger patient groups and develop clinically usable tools to help guide early treatment decisions.
Funding for the data used was provided by the National Institutes of Health and Janssen Pharmaceuticals.
