title: Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data.
  
  
  
  This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH) and healthy controls (HC). Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4) and intestinal BA signalling, as well as IM composition were assessed.
  
  
  
  53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA), chenodeoxycholic acid (CDCA) and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons). The primary to secondary BA ratio was higher in NASH compared to HC (p = 0.004), but ratio of conjugated to unconjugated BAs was not different between the groups. Bacteroidetes and Clostridium leptum counts were decreased in in a subset of 16 patients with NASH compared to 25 HC, after adjusting for body mass index and weight-adjusted calorie intake (p = 0.028 and p = 0.030, respectively). C. leptum was positively correlated with fecal unconjugated lithocholic acid (LCA) (r = 0.526, p = 0.003) and inversely with unconjugated CA (r = -0.669, p<0.0001) and unconjugated CDCA (r = - 0.630, p<0.0001). FGF19 levels were not different between the groups (p = 0.114).
  
  
  
  In adults with NAFLD, dysbiosis is associated with altered BA homeostasis, which renders them at increased risk of hepatic injury.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Marialena
authors.initials: M
authors.lastname: Mouzaki
authors.affiliation: Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Bandsma
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.|Centre for Child Nutrition Health and Development, University of Toronto, Toronto, ON, Canada.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Comelli
authors.affiliation: Toronto General Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Arendt
authors.affiliation: Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Toronto General Hospital, University Health Network, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: Toronto General Hospital, University Health Network, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Fischer
authors.affiliation: Toronto General Hospital, University Health Network, Toronto, ON, Canada.|Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Ian G
authors.initials: IG
authors.lastname: McGilvray
authors.affiliation: Toronto General Hospital, University Health Network, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Johane P
authors.initials: JP
authors.lastname: Allard
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002783:Cholestenones / Q000378:metabolism; D003430:Cross-Sectional Studies; D064806:Dysbiosis / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D011446:Prospective Studies
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; C117476:FGF19 protein, human; C000475:cholest-4-en-3-one; D005346:Fibroblast Growth Factors; D006913:Hydroxysteroid Dehydrogenases; C025376:7 alpha-hydroxysteroid dehydrogenase