Cristina Solé1, Susie Guilly2, Kevin Da Silva2, Marta Llopis1, Emmanuelle Le-Chatelier2, Patricia Huelin1, Marta Carol3, Rebeca Moreira1, Núria Fabrellas4, Gloria De Prada1, Laura Napoleone1, Isabel Graupera1, Elisa Pose1, Adrià Juanola1, Natalia Borruel5, Magali Berland2, David Toapanta6, Francesc Casellas5, Francisco Guarner5, Jöel Doré2, Elsa Solà1, Stanislav Dusko Ehrlich7, Pere Ginès8. 1. Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas (CIBEReHD), Madrid, Spain. 2. Université Paris-Saclay, INRAE (Institut National de Recherche pour l'agriculture, l'alimentation et l'environnement), Jouy en Josas, France. 3. Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. 4. Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. 5. Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas (CIBEReHD), Madrid, Spain; Digestive System Research Unit, Hospital Universitari Vall d'Hebrón, Barcelona, Spain. 6. Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 7. Université Paris-Saclay, INRAE (Institut National de Recherche pour l'agriculture, l'alimentation et l'environnement), Jouy en Josas, France. Electronic address: stanislav.ehrlich@inrae.fr. 8. Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas (CIBEReHD), Madrid, Spain. Electronic address: pgines@clinic.cat.
Abstract
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.
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.
Authors: T Oikonomou; E Cholongitas; G Gioula; F Minti; A Melidou; E Protonotariou; E Akriviadis; I Goulis Journal: Hippokratia Date: 2020 Oct-Dec Impact factor: 0.471
Authors: Amirhossein Shamsaddini; Patrick M Gillevet; Chathur Acharya; Andrew Fagan; Edith Gavis; Masoumeh Sikaroodi; Sara McGeorge; Alexander Khoruts; Somaya Albhaisi; Michael Fuchs; Richard K Sterling; Jasmohan S Bajaj Journal: Gastroenterology Date: 2021-04-20 Impact factor: 33.883
Authors: Mark M Davis; Pere Ginès; Elisa Pose; Elsa Solà; Juan J Lozano; Adrià Juanola; Julia Sidorova; Giacomo Zaccherini; Koos de Wit; Frank Uschner; Marta Tonon; Konstantin Kazankov; Cesar Jiménez; Daniela Campion; Laura Napoleone; Ann T Ma; Marta Carol; Manuel Morales-Ruiz; Carlo Alessandria; Ulrich Beuers; Paolo Caraceni; Claire Francoz; François Durand; Rajeshwar P Mookerjee; Jonel Trebicka; Victor Vargas; Salvatore Piano; Hugh Watson; Juan G Abraldes; Patrick S Kamath Journal: Hepatol Commun Date: 2021-12-28