The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis

Abstract

Intestinal fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the bowel wall. Complications, such as strictures that require surgical intervention in a large proportion of patients, are considered an inevitable consequence of chronic inflammation in inflammatory bowel disease (IBD) and leads to severe complications. The study of intestinal fibrosis in IBD has been traditionally focused on the associated immune process, and the role of the ECM itself has been largely overlooked. More recent studies have now clearly demonstrated that ECM is not simply a passive bystander of inflammation-driven fibrosis but is instead an active participant in the initiation and progression of the fibrogenic process. In this narrative review, we first describe the composition and function of the ECM components under physiological and pathological conditions of the gut. Then, we review the alterations of the intestinal ECM in IBD-associated fibrosis and the impact of fibrotic ECM on intestinal biology and function. We next critically evaluate the existing experimental systems to study the intestinal ECM, both in vitro and in vivo. We conclude by discussing the unique challenges that still exist to better understand the role of the ECM in intestinal fibrosis, and its potential diagnostic and therapeutic implications.