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Article Dans Une Revue Journal of Hepatology Année : 2017

Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice

Gladys Ferrere (1, 2, 3) , Laura Wrzosek (1, 2, 3, 4) , Frédéric Cailleux (5, 6, 4, 3) , Williams Turpin (7) , Virginie Puchois (1, 2, 3, 4) , Madeleine Spatz (8, 2, 3, 4) , Dragos Ciocan (1, 2, 3, 4) , Dominique Rainteau (9, 10, 11, 12, 13, 14, 15) , Lydie Humbert (9, 10, 16, 12, 13, 14) , Cindy Hugot (17, 6, 3, 4) , Françoise Gaudin (18, 2, 3, 4) , Marie-Louise Noordine (19) , Véronique Robert (19) , Dominique Berrebi (17, 6, 3) , Muriel Thomas (19) , Sylvie Naveau (18, 2, 3, 4, 20) , Gabriel Perlemuter (18, 2, 3, 4, 20) , Anne-Marie Cassard (21, 2, 3, 4)

Résumé

Background & Aims 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. Methods 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. Results 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. Conclusions Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD.
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hal-01608470 , version 1 (03-10-2017)

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Gladys Ferrere, Laura Wrzosek, Frédéric Cailleux, Williams Turpin, Virginie Puchois, et al.. Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice. Journal of Hepatology, 2017, 66 (4), pp.682-684. ⟨10.1016/j.jhep.2016.11.008⟩. ⟨hal-01608470⟩
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