PPARγ: The Central Mucus Barrier Coordinator in Ulcerative Colitis

Abstract

Abstract Ulcerative colitis (UC) is an idiopathic, long-term inflammatory disorder of the colon, characterized by a continuous remitting and relapsing course. The intestinal mucus barrier is the first line at the interface between the host and microbiota and acts to protect intestinal epithelial cells from invasion. Data from patients and animal studies have shown that an impaired mucus barrier is closely related to the severity of UC. Depletion of the mucus barrier is not just the strongest but is also the only independent risk factor predicting relapse in patients with UC. Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription regulator, is involved in the regulation of inflammatory cytokine expression. It is also known to promote mucus secretion under pathological conditions to expel pathogenic bacteria or toxins. More important, PPARγ has been shown to affect host-microbiota interactions by modulating the energy metabolism of colonocytes and the oxygen availability of the intestinal microbiome. It is well known that gut microbiota homeostasis is essential for butyrate generation by the commensal bacteria to supply energy resources for colonocytes. Therefore, it can be speculated that PPARγ, as a central coordinator of the mucus barrier, may be a promising target for the development of effective agents to combat UC.