Bile Acids and the Gut Microbiome as Potential Targets for NAFLD Treatment

Semi-synthetic bile acid (BA) obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, exhibited beneficial effects on non-alcoholic fatty liver disease (NAFLD). However, OCA did not cause a resolution of non-alcoholic steatohepatitis (NASH). Here we discuss several prominent knowledge gaps in BA/FXR biology. Firstly, although many groups reported elevated serum BA levels, there are reports of decreased or normal serum BA levels in NAFLD, underlining the complexity of BA regulation by environmental and genetic factors. Secondly, conflicting data exist in animal studies regarding the effects of FXR signaling on obesity and associated metabolic abnormalities. Thirdly, it remains obscure how the gut microbiome and the BA pool interact and influence the pathogenesis of NAFLD. Lastly, it is not known how FXR mediated signaling interact with G protein-coupled bile acid receptor 1 mediated signaling. Answering these questions may lead to an improved pharmaceutical intervention for NAFLD targeting the FXR signaling pathway. Address correspondence and reprint requests to Lixin Zhu, Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, 3435 Main Street, 422BRB, Buffalo, NY14214 (e-mail: lixinzhu@buffalo.edu); Susan S. Baker (e-mail: sbaker@upa.chob.edu) Received 7 August, 2017 Accepted 27 March, 2018 Conflict of Interest and Source of Funding: The authors declare that no conflict of interest exists. This work was supported by GEM Community of Excellence, the University at Buffalo (LZ) and the Tommy and Peter Fund, Inc., Buffalo, NY (SSB and LZ). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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