Unique Biological Fingerprint Indicates Lower Progression Risk of Crohn’s Disease

Mild Crohn’s disease affects nearly one in four patients, yet most research has focused on moderate to severe forms of the disease. This has led to a gap in understanding and treatment for patients with less aggressive symptoms. Many patients are prescribed advanced therapies shortly after diagnosis, which are often costly, lifelong, and come with potential side effects. However, not all patients with mild Crohn’s disease progress to severe forms, and there is currently no way to distinguish those who need aggressive treatment from those who do not. Now, a new study has identified distinct biological signatures in patients with mild Crohn’s disease, offering a path toward more personalized, less aggressive treatment strategies that avoid overtreatment and reduce unnecessary side effects.

This first-of-its-kind study by researchers at the Mount Sinai Health System (New York City, NY, USA) used multi-omics data to investigate the biology of mild Crohn’s disease. Multi-omics combines information from genes, proteins, and metabolites to provide a more complete understanding of disease mechanisms. The team analyzed data from two patient cohorts—the Mount Sinai Crohn’s and Colitis Registry and the Ocean State Crohn’s and Colitis Area Registry. Their findings revealed that patients with mild Crohn’s disease had a reduced immune response and altered sphingolipid metabolism, a process linked to immune regulation. These features formed a biological fingerprint distinct from more aggressive disease types and were associated with a lower risk of disease progression.

The findings, published in Gastroenterology, suggest that these biomarkers could help predict which patients are likely to have a stable, mild disease course. This opens the door to delaying or avoiding biologic therapies, potentially reducing side effects, healthcare costs, and medication exposure for patients with milder conditions. The researchers now plan to validate these biomarkers in larger, more diverse populations and develop clinical tools to guide early treatment decisions. The study marks a major step toward precision medicine in inflammatory bowel disease and could reshape how Crohn’s disease is managed in everyday practice.

"We hope to develop tools that help physicians predict which patients are likely to have a mild, stable disease course. 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," said Jean-Frédéric Colombel, MD, co-author of the study.