A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease

Abstract

The presence of cirrhosis in nonalcoholic-fatty-liver-disease (NAFLD) is the most important predictor of liver-related mortality. Limited data exist concerning the diagnostic accuracy of gut-microbiome-derived signatures for detecting NAFLD-cirrhosis. Here we report 16S gut-microbiome compositions of 203 uniquely well-characterized participants from a prospective twin and family cohort, including 98 probands encompassing the entire spectrum of NAFLD and 105 of their first-degree relatives, assessed by advanced magnetic-resonance-imaging. We show strong familial correlation of gut-microbiome profiles, driven by shared housing. We report a panel of 30 features, including 27 bacterial features with discriminatory ability to detect NAFLD-cirrhosis using a Random Forest classifier model. In a derivation cohort of probands, the model has a robust diagnostic accuracy (AUROC of 0.92) for detecting NAFLD-cirrhosis, confirmed in a validation cohort of relatives of proband with NAFLD-cirrhosis (AUROC of 0.87). This study provides evidence for a fecal-microbiome-derived signature to detect NAFLD-cirrhosis.

Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis

“…In an initial study determining metabolites and composition, there was a clear difference between patients with and without cirrhosis. 85 In the first metagenomics study, Proteobacteria increased with worsening fibrosis in NAFLD and at the species level, Eubacterium rectale, Ruminococcus obeum CAG: 39, were the most abundant organisms in mild/moderate NAFLD while B. vulgatus and E. coli were the most abundant in advanced fibrosis. 85 This was subsequently extended to a larger population, albeit from the same centre, with 30 factors (including 27 bacteria and remaining metabolites) as differentiators.…”

Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease

“…There have been recent advances in using bacterial taxonomy to predict NAFLD disease states 55 ; however, evidence of functional redundancy between different microbial taxa linked to proinflammatory pathways suggests that genes, rather than taxa, are likely to prove better biomarkers for the identification and characterization of NAFLD. Accordingly, we found that genus abundance measurements were inadequate for predicting disease using CART.…”

Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives

“…NAFLD patients have a higher prevalence of dysbiosis with increased Bacteroides , Escherichia , and Ruminococcus , and decreased Prevotella bacteria in those with advanced forms of the disease, indicating an association between Gram­negative bacteria and progression of liver fibrosis . Additionally, fecal‐microbiome‐derived signatures associated with fibrotic NASH and NAFLD‐related cirrhosis have been described . Also, a significant association between NAFLD and SIBO has been established .…”