Extracellular Matrix Remodeling in Inflammatory Bowel Disease: From Pre-Symptomatic Changes to Active Flares

Inflammatory bowel disease (IBD) is increasingly recognized as a disorder in which extracellular matrix (ECM) remodeling is not merely a downstream consequence of mucosal inflammation but a potential significant contributor in pathogenesis. The intestinal ECM regulates epithelial barrier integrity, immune cell trafficking and the resolution of inflammation. Evidence derived predominantly from murine models demonstrates that structural, compositional and mechanical alterations may emerge before clinical symptoms. This pre-symptomatic state is characterized by subclinical immune infiltration and elevated matrix remodeling enzyme activity within the intestinal epithelium. During active disease, remodeling intensifies, with increased matrix metalloproteinase activity generating ECM fragments that reflect endoscopic severity and may discriminate flares from remission. This review synthesizes the evidence on ECM remodeling during the pre-symptomatic and flare phases, emphasizing the ECM as an active driver of early inflammation. Recognizing this early window opens opportunities for diagnostic and therapeutic strategies beyond the current focus on established mucosal inflammation.