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Gut. 2016 May;65(5):830-9. doi: 10.1136/gutjnl-2015-310585. Epub 2015 Dec 7.

Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.

Author information

1
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.
2
INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
3
INRA, UMR1319 Micalis, Jouy-en-Josas, France AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
4
Faculté de Médecine, Aix-Marseille University, Marseille, France INSERM, UMR1062 NORT, Marseille, France.
5
INRA, UMR 1313, GABI-LGS Plateforme ICE, Jouy-en-Josas, France.
6
Department of Gastroenterology, Digestive System Research Unit, Hospital University Vall d'Hebron and VHIR, UAB, Spain.
7
IPSIT, IFR141, Faculté de Pharmacie, Univ Paris-Sud, Châtenay-Malabry, France.
8
AP-HP, Hôpital Bicêtre, Unité de recherche clinique Paris-Sud, Kremlin-Bicêtre, France.
9
Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France AP-HP, Anatomie-pathologique, Hôpital Antoine-Béclère, Clamart, France.
10
INSERM UMR996-Inflammation, Chemokines and Immunopathology, Clamart, France AP-HP, Anatomie et de Cytologie Pathologiques, Hôpital Robert Debré, Paris, France.
11
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.
12
Université Clermont Auvergne, Institut de Chimie de Clermont-Ferrand UMR CNRS 6296, Clermont-Ferrand, France.

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).

DESIGN:

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.

KEYWORDS:

ALCOHOL; ALCOHOLIC LIVER DISEASE; INTESTINAL MICROBIOLOGY; LIVER

PMID:
26642859
DOI:
10.1136/gutjnl-2015-310585
[Indexed for MEDLINE]

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