Dataset Information

A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis.

ABSTRACT: Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, area under curve [AUC]). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species might offer universal utility as a non-invasive diagnostic test for cirrhosis.

SUBMITTER: Oh TG

PROVIDER: S-EPMC7822714 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis.

Oh Tae Gyu TG Kim Susy M SM Caussy Cyrielle C Fu Ting T Guo Jian J Bassirian Shirin S Singh Seema S Madamba Egbert V EV Bettencourt Ricki R Richards Lisa L Yu Ruth T RT Atkins Annette R AR Huan Tao T Brenner David A DA Sirlin Claude B CB Downes Michael M Evans Ronald M RM Loomba Rohit R

Cell metabolism 20200630 5

Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning alg ...[more]

PMID: 32610095

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Project description:BackgroundThere are limited data on the diagnostic accuracy of gut microbial signatures for predicting hepatic decompensation in patients with cirrhosis.AimsTo determine whether a stool metagenome-derived signature accurately detects hepatic decompensation and mortality risk in cirrhosis secondary to non-alcoholic fatty liver disease (NAFLD) METHODS: Shotgun metagenomic sequencing was performed on faecal samples collected at study entry from a prospective cohort of adults with NAFLD-related cirrhosis. A Random Forest machine learning algorithm was utilised to identify a metagenomic signature of decompensated cirrhosis (defined by ascites, hepatic encephalopathy or variceal haemorrhage) and subsequently validated in an external cohort. A Cox proportional hazards regression model was used to examine predictors of all-cause mortality.ResultsIn all, 25 adults with NAFLD-related cirrhosis (training cohort) were included. Among the 16 participants with decompensated cirrhosis, 33% had ascites, 56% had hepatic encephalopathy and 22% had experienced a variceal haemorrhage (not mutually exclusive). We identified a stool metagenomic signature comprising 13 discriminatory species that reliably distinguished decompensated NAFLD-related cirrhosis (diagnostic accuracy, 0.97, 95% confidence interval [CI] 0.96-0.99). Diagnostic accuracy of the 13-species signature remained high after adjustment for lactulose (area under the curve [AUC] 0.99) and rifaximin use (AUC 0.93). The discriminative ability of 13-species metagenomic signature was robust in an independent test cohort (AUC 0.95, 95% CI 0.81-1.00). The 13-species metagenomic signature (hazard ratio [HR] 1.54, 95% CI 1.10-2.15, p = 0.01) was a stronger predictor of mortality than the Model for End-Stage Liver Disease score (HR 1.25, 95% CI 1.03-1.53, p = 0.03).ConclusionsThis study provides evidence for a gut metagenome-derived signature with high diagnostic accuracy for hepatic decompensation that predicts risk of mortality in NAFLD-related cirrhosis.

Dataset Information

A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis.

Publications

A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis.

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