title: Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration.
abstract: OBJECTIVE
  All-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)-induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration.
  
  
  METHODS
  C57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied.
  
  
  RESULTS
  RA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (>85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers.
  
  
  CONCLUSIONS
  Priming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation.
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: Hui-Xin
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D064307:Microbiota; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D019394:Ki-67 Antigen; C414620:fibroblast growth factor 21; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1
keywords: Pathology Section; energy metabolism; fibroblast growth factor 21; gut-liver axis; lipid homeostasis; partial hepatectomy