| Abstract: | Maintaining bile acid (BA) homeostasis is important and regulated by BA activated receptors and signaling pathways. Farnesoid X receptor (FXR) and its regulated target networks in both the liver and the intestines are critical in suppressing BA synthesis and promoting BA enterohepatic circulation. In addition, FXR is critical in regulating lipid metabolism and reducing inflammation, processes critical in the development of cholestasis and fatty liver diseases. Moreover, BAs are modulated by and regulate gut microflora. Xenobiotic exposure could affect liver disease development. However, the effects and the mechanisms by which xenobiotics interact with FXR and then regulate BA homeostasis are only emerging. In this minireview, our focus is to provide evidence from reports that study the effects of xenobiotic exposure on altering homeostasis and functions of BAs and FXR. Understanding these effects will help to determine liver disease pathogenesis and provide better prevention and treatment in the future. Significance Statement Environmental chemical exposure significantly contributes to the development of cholestasis and non-alcoholic steatohepatitis. The impact of exposures on bile acid signaling and Farnesoid X receptor-mediated gut-liver crosstalk is emerging. However, there is still a huge gap in understanding on how these chemicals contribute to the dysregulation of bile acid homeostasis and how this dysregulation may promote the development of liver diseases. |
