Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis

Background and Aims: Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigat...

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Detalles Bibliográficos
Autores: Solé Padullés, Cristina, Guilly, Susie, Da Silva, Kevin, Llopis, Marta, Le-Chatelier, Emmanuelle, Huelin, Patricia, Carol, Marta, Moreira, Rebeca, Fabrellas i Padrès, Núria, de la Prada, Gloria, Napoleone, Laura, Graupera, Isabel, Pose Méndez, Elisa, Juanola Mayos, Adrià, Borruel, Natalia, Berland, Magali, Toapanta, David, Casellas, Francesc, Guarner, Francisco, Doré, Jöel, Solà, Elsa, Ehrlich, Stanislav Dusko, Ginès i Gibert, Pere
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175249
Acceso en línea:https://hdl.handle.net/2445/175249
Access Level:acceso abierto
Palabra clave:Cirrosi hepàtica
Insuficiència hepàtica
Microbiota intestinal
Hepatic cirrhosis
Liver failure
Gastrointestinal microbiome
Descripción
Sumario:Background and Aims: Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigated the gut microbiome in patients with cirrhosis encompassing the whole spectrum of disease (compensated, acutely decompensated without ACLF, and ACLF). A group of healthy subjects was used as control subjects. Methods: Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing were performed using the Ion Proton Sequencer (ThermoFisher Scientific, Waltham, MA). Microbial genes were grouped into clusters, denoted as metagenomic species. Results: Cirrhosis was associated with a remarkable reduction in gene and metagenomic species richness compared with healthy subjects. This loss of richness correlated with disease stages and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic therapy. ACLF was associated with a significant increase of Enterococcus and Peptostreptococcus sp and a reduction of some autochthonous bacteria. Gut microbiome alterations correlated with model for end-stage liver disease and Child-Pugh scores and organ failure and was associated with some complications, particularly hepatic encephalopathy and infections. Interestingly, gut microbiome predicted 3-month survival with good stable predictors. Functional analysis showed that patients with cirrhosis had enriched pathways related to ethanol production, γ-aminobutyric acid metabolism, and endotoxin biosynthesis, among others. Conclusions: Cirrhosis is characterized by marked alterations in gut microbiome that parallel disease stages with maximal changes in ACLF. Altered gut microbiome was associated with complications of cirrhosis and survival. Gut microbiome may contribute to disease progression and poor prognosis. These results should be confirmed in future studies.

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