The complex relationship between microbiota, immune response and creeping fat in Crohn's disease.

In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease, known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of Crohn's disease. The transmural inflammation of Crohn's disease facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to the activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these Crohn's disease-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in the regulation of immune response, adipogenesis and the maintenance of barrier function, as well as on the creeping fat production of inflammatory influencers such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of Crohn's disease and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for Crohn's disease. We aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of Crohn's disease with the development of creeping fat.