Titre :

Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease

Auteur(s) :

Duan, Yi [Auteur]
Llorente, Cristina [Auteur]
Lang, Sonja [Auteur]
Brandl, Katharina [Auteur]
Chu, Huikuan [Auteur]
Jiang, Lu [Auteur]
White, Richard C. [Auteur]
Clarke, Thomas H. [Auteur]
Nguyen, Kevin [Auteur]
Torralba, Manolito G. [Auteur]
Shao, Yan [Auteur]
Liu, Jinyuan [Auteur]
Hernandez-Morales, Adriana [Auteur]
Lessor, Lauren [Auteur]
Rahman, Imran R. [Auteur]
Miyamoto, Yukiko [Auteur]
Ly, Melissa [Auteur]
Gao, Bei [Auteur]
Sun, Weizhong [Auteur]
Kiesel, Roman [Auteur]
Hutmacher, Felix [Auteur]
Lee, Suhan [Auteur]
Ventura-Cots, Meritxell [Auteur]
Bosques-Padilla, Francisco [Auteur]
Verna, Elizabeth C. [Auteur]
Abraldes, Juan G. [Auteur]
Brown, Robert S. [Auteur]
Vargas, Victor [Auteur]
Altamirano, Jose [Auteur]
Caballeria, Juan [Auteur]
Shawcross, Debbie [Auteur]
Ho, Samuel B. [Auteur]
Louvet, Alexandre [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lucey, Michael R. [Auteur]
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Garcia-Tsao, Guadalupe [Auteur]
Bataller, Ramon [Auteur]
Tu, Xin M. [Auteur]
Eckmann, Lars [Auteur]
Van Der Donk, Wilfred A. [Auteur]
Young, Ry [Auteur]
Lawley, Trevor D. [Auteur]
Starkel, Peter [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Pride, David [Auteur]
Fouts, Derrick E. [Auteur]
Schnabl, Bernd [Auteur]

Titre de la revue :

Nature

Nom court de la revue :

Nature

Numéro :

575

Pagination :

505–511

Date de publication :

2019-11-21

ISSN :

1476-4687

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1,2,3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The ...
Lire la suite >Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1,2,3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin—a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6—as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Date de dépôt :

2024-01-30T10:27:18Z
2024-04-30T08:46:35Z