ALTERATIONS IN GUT MICROBIOME IN CIRRHOSIS AS ASSESSED BY QUANTITATIVE METAGENOMICS. RELATIONSHIP WITH ACUTE-ON-CHRONIC LIVER FAILURE AND PROGNOSIS.

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Cirrhosis is associated with changes in gut microbiome composition. Although ACLF is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. To investigate 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 controls.Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing was performed using the Ion Proton sequencer. Microbial genes were grouped into clusters, denoted as metagenomic species(MGS).Cirrhosis was associated with a remarkable reduction in gene and MGS richness compared to 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 reduction of some autochthonous bacteria. Gut microbiome alterations correlated with MELD and Child-Pugh scores and organ failures 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, GABA metabolism, and endotoxin biosynthesis, among others.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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