title: Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.
abstract: OBJECTIVE
  There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH).
  
  
  METHODS
  We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied.
  
  
  RESULTS
  A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+)T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions.
  
  
  CONCLUSIONS
  Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: M
authors.initials: M
authors.lastname: Llopis
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Cassard
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
authors.forename: L
authors.initials: L
authors.lastname: Wrzosek
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: L
authors.initials: L
authors.lastname: Boschat
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: A
authors.initials: A
authors.lastname: Bruneau
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
authors.forename: G
authors.initials: G
authors.lastname: Ferrere
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
authors.forename: V
authors.initials: V
authors.lastname: Puchois
authors.affiliation: Faculté de Médecine, Aix-Marseille University, Marseille, France INSERM, UMR1062 NORT, Marseille, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Martin
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: P
authors.initials: P
authors.lastname: Lepage
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: T
authors.initials: T
authors.lastname: Le Roy
authors.affiliation: INRA, UMR 1313, GABI-LGS Plateforme ICE, Jouy-en-Josas, France.
authors.forename: L
authors.initials: L
authors.lastname: Lefèvre
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: B
authors.initials: B
authors.lastname: Langelier
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
authors.forename: F
authors.initials: F
authors.lastname: Cailleux
authors.affiliation: Department of Gastroenterology, Digestive System Research Unit, Hospital University Vall d'Hebron and VHIR, UAB, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: González-Castro
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: S
authors.initials: S
authors.lastname: Rabot
authors.affiliation: IPSIT, IFR141, Faculté de Pharmacie, Univ Paris-Sud, Châtenay-Malabry, France.
authors.forename: F
authors.initials: F
authors.lastname: Gaudin
authors.affiliation: AP-HP, Hôpital Bicêtre, Unité de recherche clinique Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: H
authors.initials: H
authors.lastname: Agostini
authors.affiliation: Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France AP-HP, Anatomie-pathologique, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: S
authors.initials: S
authors.lastname: Prévot
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France AP-HP, Anatomie et de Cytologie Pathologiques, Hôpital Robert Debré, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Berrebi
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: D
authors.initials: D
authors.lastname: Ciocan
authors.affiliation: Université Clermont Auvergne, Institut de Chimie de Clermont-Ferrand UMR CNRS 6296, Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Jousse
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: S
authors.initials: S
authors.lastname: Naveau
authors.affiliation: INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: P
authors.initials: P
authors.lastname: Gérard
authors.affiliation: INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: G
authors.initials: G
authors.lastname: Perlemuter
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000382:microbiology; D064806:Dysbiosis / Q000150:complications*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: ALCOHOL; ALCOHOLIC LIVER DISEASE; INTESTINAL MICROBIOLOGY; LIVER