RT Journal Article
SR Electronic
T1 Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 830
OP 839
DO 10.1136/gutjnl-2015-310585
VO 65
IS 5
A1 M Llopis
A1 A M Cassard
A1 L Wrzosek
A1 L Boschat
A1 A Bruneau
A1 G Ferrere
A1 V Puchois
A1 J C Martin
A1 P Lepage
A1 T Le Roy
A1 L Lefèvre
A1 B Langelier
A1 F Cailleux
A1 A M González-Castro
A1 S Rabot
A1 F Gaudin
A1 H Agostini
A1 S Prévot
A1 D Berrebi
A1 D Ciocan
A1 C Jousse
A1 S Naveau
A1 P Gérard
A1 G Perlemuter
YR 2016
UL http://gut.bmj.com/content/65/5/830.abstract
AB 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.