Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ

The pathophysiological processes of inflammatory bowel diseases (IBDs), i.e., Crohn's disease (CD) and ulcerative colitis (UC), are still not completely understood. The exact etiology remains unknown, but it is well established that the pathogenesis of the inflammatory lesions is due to a dysregulation of the gut immune system resulting in over-production of pro-inflammatory cytokines. Increasing evidence underlines the involvement of both environmental and genetic factors. Regarding the environment, the microbiota seems to play a crucial role. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert pleiotropic effects on glucose homeostasis, lipid metabolism, inflammatory/immune processes, cell proliferation, and fibrosis. Furthermore, PPARs modulate interactions with several environmental factors, including microbiota. A significantly impaired PPAR gamma expression was observed in UC patients' colonic epithelial cells, suggesting that the disruption of PPAR gamma signaling may represent a critical step of the IBD pathogenesis. This paper will focus on the role of PPAR gamma in the interaction between environmental factors and IBD, and it will analyze the most suitable in vitro and in vivo models available to better study these relationships.

Automated summary

The pathophysiological processes of inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are not fully understood, but dysregulation of the gut immune system leading to overproduction of pro-inflammatory cytokines is a key factor. Both environmental and genetic factors are involved, with the microbiota playing a crucial role. PPARγ modulates interactions with environmental factors, and its impaired expression may represent a critical step in IBD pathogenesis, particularly in ulcerative colitis.