Mechanisms and models for intestinal fibrosis in IBD

Intestinal fibrosis is a common outcome in IBD leading to significant morbidity that, to date, has no effective medical treatment. Current knowledge regarding potential mechanism(s) of intestinal fibrogenesis and stricture formation is limited, due in large part to the lack of relevant animal models. Although conventional models possess aspects that are advantageous to study specific mechanisms involved in gut fibrosis, most lack the features of a spontaneously occurring process leading to the formation of intestinal fibrotic lesions following mucosal inflammatory events and the ability to investigate the natural course of disease over time. This review aims to discuss established and novel animal models of gut fibrosis, particularly focusing on the advantages and disadvantages of each model system and the insights they bring to our understanding of the mechanisms of fibrogenesis. In fact, recent enhancements to existing models and the expansion of novel animal models of gut fibrosis is opening up multiple avenues for investigation which should stimulate progress in our mechanistic understanding of intestinal fibrogenesis and facilitate the development of effective pharmacotherapy in an area of significant unmet need.