RECENT ADVANCE IN BASIC SCIENCE
Liver–gut axis and farnesoid X receptor nexus
Nadia Panera, Anna Alisi
1Unità di Ricerca di Genetica Molecolare dei Caratteri Complessi, Ospedale Pediatrico Bambino Gesù e IRCCS di Roma.
FXR is a nuclear receptor mainly dedicated to the regulation of signaling up-stream the bile acid synthesis. This receptor is expressed in both liver and gut, and mediates several integrated networks between these two organs. The molecular network is represented by redundant mechanisms that repress the transcription of CYP7A1 gene that encodes for the cholesterol 7α-hydroxylase first and rate limiting step in bile acid synthesis. Bile acids are toxic for the organism, in fact, their accumulation and defects in FXR pathway have been found in different hepatopathies, including progressive familial intrahepatic cholestasis (PFIC) and non-alcoholic fatty liver disease (NAFLD). Several lines of experimental evidence demonstrated that the presence of FXR is crucial for liver regeneration and exerts protective anti-inflammatory and anti-fibrotic properties. Therefore, FXR agonists, such as obeticholic acid, that were approved for the treatment of primary sclerosing cholangitis, may represent an attractive class of drugs also for children affected by NAFLD and PFIC. In this review we overview the role of FXR in the regulation of the entheropatic circle of bile acids by the establishment of a liver-cut axis.