Early Prediction and the Path Toward Prevention in Crohn’s Disease, With Sun-Ho Lee, MD, PhD

As evidence grows that Crohn’s disease begins years before symptoms appear, research is moving beyond early detection to what intervention might be possible. Identifying immune signals that precede disease onset raises critical questions about mechanism, causality, and whether these pathways can be modified to reduce risk, shifting the field toward prediction and prevention.

In a recent study, Sun-Ho Lee, MD, PhD, a gastroenterologist at Sinai Health Zane Cohen Centre for Digestive Diseases, and colleagues identified a blood test that can predict Crohn’s disease years before symptoms appear by measuring a person’s immune response to flagellin. They followed 381 first-degree relatives of Crohn’s patients as part of the Genetic, Environmental, and Microbial (GEM) Project, 77 of whom went on to develop the disease. Additional assay-based analyses revealed 19 of 49 IgG antimicrobial antibody responses were significantly associated with the risk of Crohn’s.

Check out part 1 of Lee’s interview with HCPLive Gastroenterology on preclinical Crohn’s and his research here.

“With these 2 assays, especially the second one, we were able to show with an alternative assay, that it is one of the strong, key, crucial signals coming from the immune response against the hinge region of the flagellin,” Lee told HCPLive.

At the same time, he was careful to underscore the many unanswered questions that remain. It is still unclear why some individuals develop antibodies to these flagellins before disease onset, or whether this reflects a failure of immune tolerance, increased microbial translocation across a compromised gut barrier, or another upstream trigger altogether. He noted that disentangling these mechanisms will require additional work.

Despite these unknowns, Lee described vaccination as an interesting possibility that emerges from narrowing the immune signal to a specific epitope. He pointed to prior animal studies demonstrating that vaccination against Salmonella flagellin can protect against colitis, as well as work showing that CD4+ T-cell responses to flagellins can be modulated in experimental models.

Based on this body of evidence, Lee and colleagues hypothesize that targeting pathogenic flagellin responses through vaccination could, in theory, blunt their role in Crohn’s disease development. He stressed, however, that this idea remains speculative and would require validation.

“There is really a growing interest in this early prediction and prevention in the field of IBD,” Lee said, describing other research groups and ongoing projects seeking to advance the field’s understanding of early disease.

Editors’ Note: Lee reports no relevant disclosures.

References

1. Wu RY, Xue M, Zhao Q, et al. Serum IgG Response to a Conserved Domain of Commensal Flagellins Predicts Future Risk of Crohn's Disease in First-degree Relatives. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2025.12.006

2. Lunenfeld-Tanenbaum Research Institute. A simple blood test can predict Crohn’s disease years before symptoms appear. EurekAlert! https://www.eurekalert.org/news-releases/1111855