title: Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice.
abstract: Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD.
  
  
  
  Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period.
  
  
  
  Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis.
  
  
  
  Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD.
  
  
  
  Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human ALD through intestinal microbiota manipulation.
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Gladys
authors.initials: G
authors.lastname: Ferrere
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Wrzosek
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cailleux
authors.affiliation: Division of Gastroenterology, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada; Department of Medicine, University of Toronto, ON M5S 1A8, Canada.
authors.forename: Williams
authors.initials: W
authors.lastname: Turpin
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Puchois
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Spatz
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Dragos
authors.initials: D
authors.lastname: Ciocan
authors.affiliation: Sorbonne Universités, UPMC Université Paris 6, Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), INSERM-ERL 1157, Paris, France; UMR 7203 Laboratoire des Biomolécules, UPMC/CNRS/ENS, Paris, France; Département PM2 Plateforme de Métabolomique, APHP, Hôpital Saint Antoine, Peptidomique et dosage de Médicaments, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.affiliation: Sorbonne Universités, UPMC Université Paris 6, Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), INSERM-ERL 1157, Paris, France; UMR 7203 Laboratoire des Biomolécules, UPMC/CNRS/ENS, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Humbert
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Hugot
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gaudin
authors.affiliation: INRA, UMR 1319 MICALIS, AgroParisTech, Jouy-en-Josas, France.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Noordine
authors.affiliation: INRA, UMR 1319 MICALIS, AgroParisTech, Jouy-en-Josas, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Robert
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; AP-HP, Anatomie et de Cytologie Pathologiques, Hôpital Robert Debré, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.affiliation: INRA, UMR 1319 MICALIS, AgroParisTech, Jouy-en-Josas, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Thomas
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Naveau
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Perlemuter
authors.affiliation: INSERM U996, DHU Hepatinov, Univ Paris-Sud, Université Paris-Saclay, 92140 Clamart, France; Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), IFR141, Faculté de Pharmacie, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France. Electronic address: cassard.doulcier@u-psud.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cassard
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism; D004043:Dietary Fiber / Q000008:administration & dosage; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000382:microbiology; D064806:Dysbiosis / Q000382:microbiology* / Q000517:prevention & control*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000382:microbiology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010368:Pectins / Q000008:administration & dosage; D056692:Prebiotics / Q000008:administration & dosage
chemical_list: D001647:Bile Acids and Salts; D004043:Dietary Fiber; D056692:Prebiotics; D010368:Pectins
keywords: Alcohol drinking; Bacteroides; Dysbiosis; Fatty liver; Fecal microbiota transplantation; Gastrointestinal microbiome; Liver diseases, alcoholic; Microbiota; Prebiotic