Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD). While inflammation is a prerequisite for initiating fibrosis, it does not fully explain its progression, which often continues despite effective anti-inflammatory treatment. This suggests that fibrotic mechanisms evolve from an inflammation-dependent priming phase to a self-perpetuating phase that can operate independently of ongoing inflammation. While the former has been widely studied, the latter remains underexplored. In this context, this review summarizes the current evidence on the self-perpetuating mechanisms driving fibrosis in IBD, even after inflammation resolves. We delve into key drivers such as genetic predisposition, extracellular matrix microenvironment, creeping fat, and metabolic reprogramming. The aim is to enhance understanding of this self-sustaining cycle and encourage further research to advance treatment strategies for IBD-related fibrosis.