Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Disease and Perspectives for Therapeutic Implication

BACKGROUND: Intestinal fibrosis with stricture formation is a common feature of inflammatory bowel disease (IBD) and leads to a significantly impaired quality of life in affected patients, intestinal obstruction as well as to the need for surgical intervention. This constitutes a major treatment challenge. Key Messages: Fibrosis results from the response of gut tissue to the insult inflicted by chronic inflammation. Similarly to what occurs in other organs, the underlying fibrogenic mechanisms are complex and dynamic, involving multiple cell types, interrelated cellular events, and a large number of soluble factors. Owing to a breakdown of the epithelial barrier in IBD, luminal bacterial products leak into the interstitium and induce an innate immune response mediated by the activation of both immune and non-immune cells. Other environmental factors as well as chronic inflammation will certainly impact the quality and quantity of intestinal fibrosis. Finally, the composition of the intestinal extracellular matrix is dramatically altered in chronic gut inflammation and actively promotes fibrosis through its mechanical properties. The conventional view that intestinal fibrosis is an inevitable and irreversible process is gradually changing in light of an improved understanding of the cellular and molecular mechanisms that underline its pathogenesis. In addition, clinical observations in patients who undergo strictureplasty have shown that stricture formation is reversible. CONCLUSIONS: Identification of the unique mechanisms of intestinal fibrogenesis should create a practical framework to target and block specific fibrogenic pathways, estimate the risk of fibrotic complications, permit the detection of early fibrotic changes and, eventually, allow the development of treatment methods customized to each patient's type and degree of intestinal fibrosis.