Open AccessBile Acids and the Gut Microbiome as Potential Targets for NAFLD Treatment
Author(s) -
Zhu Lixin,
Baker Robert D.,
Zhu Ruixin,
Baker Susan S.
Publication year - 2018
Publication title -
journal of pediatric gastroenterology and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 131
eISSN - 1536-4801
pISSN - 0277-2116
DOI - 10.1097/mpg.0000000000002010
Subject(s) - obeticholic acid , farnesoid x receptor , nonalcoholic fatty liver disease , bile acid , medicine , nonalcoholic steatohepatitis , microbiome , gut flora , ursodeoxycholic acid , agonist , nuclear receptor , receptor , bioinformatics , disease , fatty liver , biochemistry , biology , transcription factor , immunology , gene
Semisynthetic bile acid (BA) obeticholic acid, a potent farnesoid X receptor (FXR) agonist, exhibited beneficial effects on nonalcoholic fatty liver disease (NAFLD). Obeticholic acid, however, did not cause a resolution of nonalcoholic steatohepatitis. 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 BA receptor 1–mediated signaling. Answering these questions may lead to an improved pharmaceutical intervention for NAFLD targeting the FXR signaling pathway.