Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Sustained, transmural inflammation of the bowel wall may result in the development of a fistula in Crohn's disease (CD). Fistula formation is a recognised complication and cause of morbidity, occurring in 40% of patients with CD. Despite advanced treatment, one third of patients experience recurrent fistulae. Development of targeting treatment for fistulae will be dependent on a more in depth understanding of its pathogenesis. Presently, pathogenesis of CD-associated fistulae remains poorly defined, in part due to the lack of accepted in vitro tissue models recapitulating the pathogenic cellular lesions linked to fistulae and limited in vivo models. This review provides a synthesis of the existing knowledge of the histopathological, immune, cellular, genetic and microbial contributions to the pathogenesis of CD-associated fistulae including the widely accredited contribution of epithelial-to-mesenchymal transition, upregulation of matrix metalloproteinases and overexpression of invasive molecules resulting in tissue remodelling and subsequent fistula formation. We conclude by exploring how we might utilise advancing technologies to verify and broaden our current understanding whilst exploring novel causal pathways to provide further inroads to future therapeutic targets.

Original publication




Journal article


Cell Mol Gastroenterol Hepatol

Publication Date



Crohn’s-associated fistula, Penetrating, epithelial-to-mesenchymal transition, model systems