Metabolic modulation during intestinal fibrosis

Abstract

Intestinal fibrosis is one of the biggest challenges in the therapeutic management of inflammatory bowel diseases (IBD). Patients with Crohn's disease, in particular, suffer from fibrotic complications, which are manifested by the clinical stenosis of the bowel. Although fibrosis is caused by recurrent episodes of inflammation and wound healing, current therapies for IBD do not seem to reduce the incidence of stenosis, suggesting that inflammation-independent mechanisms also contribute to intestinal fibrogenesis. The lack of anti-fibrotic therapies for IBD and the huge burden this complication places on patients has prompted us to redirect inflammation research toward understanding the mechanisms that drive gut fibrosis. Based on data from other fibroproliferative diseases, metabolic modifications are increasingly recognized as pathogenic processes that may generate new therapeutic opportunities. These metabolic alterations result from a switch in the cellular metabolism of activated fibroblasts, which are the key mediator cells of fibrosis. Here, we review the metabolic changes associated with fibrotic disease and summarize the evidence of a metabolic shift during intestinal fibrosis.

Keywords: fatty acid metabolism; fibroblasts; glutaminolysis; glycolysis; intestinal fibrosis; metabolic reprogramming.