New Research Uncovers Factors that Contribute to Fistulas

Perianal fistulizing Crohn’s disease (PCD) is a complication of Crohn’s that affects up to 40% of Crohn’s patients. Fistulas form when abnormal connections form between the intestine and surrounding tissue.  Specifically, in the presence of inflammation, ulcers extend through the entire intestinal wall, creating a tunnel that drains pus away from the inflamed area. Fistulas may occur anywhere along the GI tract and are very painful and difficult to treat.

In good news for patients, a 2025 study published in The Journal of Clinical Investigation identifies new factors that contribute to fistulas. Examining samples of patients with PCD, researchers found that a specific immune signal--interferon gamma (IFN-γ)—was highly active in patients with PCD. This over-activation was linked to inflammation and changes in tissue that allow fistulas to form and persist.

The study also identified high numbers of a type of white blood cell, Th17 immune cells, which help protect the body from infections. In PCD, however, these cells produced large amounts of IFN-γ, fueling inflammation and tissue damage. Together with other immune cells, they created a cycle that drives fistula formation.  Combined, these new findings may pave the way for more effective treatments of fistulas and much needed relief for patients.

References

​Crohn’s & Colitis Foundation

Revealing hyperactivated IFN-γ pathways in perianal fistulizing Crohn’s disease using single-cell and spatial multi-omics, J Clin Invest. 2025; 135(17):e193413.