title: The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota.
abstract: Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Fifty-seven patients with biopsy-proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism.
  
  
  CONCLUSIONS
  NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre-/probiotics therapies.
authors.affiliation: Hepato-Gastroenterology Department, University Hospital, Angers, France.|HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boursier
authors.affiliation: Center for Genomics of Microbial Systems, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mueller
authors.affiliation: INRA, UMR1345 Institut de Recherches en Horticulture et Semences, SFR4207 QUASAV, Beaucouzé, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Barret
authors.affiliation: Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Mariana
authors.initials: M
authors.lastname: Machado
authors.affiliation: HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Fizanne
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Felix
authors.initials: F
authors.lastname: Araujo-Perez
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC.
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Guy
authors.affiliation: Center for Genomics of Microbial Systems, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.|Department of Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Seed
authors.affiliation: Center for Genomics of Microbial Systems, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
authors.forename: John F
authors.initials: JF
authors.lastname: Rawls
authors.affiliation: Center for Genomics of Microbial Systems, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: David
authors.affiliation: HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hunault
authors.affiliation: Hepato-Gastroenterology Department, University Hospital, Angers, France.|HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Oberti
authors.affiliation: Hepato-Gastroenterology Department, University Hospital, Angers, France.|HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D000368:Aged; D064806:Dysbiosis / Q000150:complications* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D005355:Fibrosis; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000382:microbiology* / Q000473:pathology