Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease

Cell Metab. 2017 May 2;25(5):1054-1062.e5. doi: 10.1016/j.cmet.2017.04.001.


The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0-2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD.

Keywords: NASH; biomarker; cirrhosis; fatty liver; fibrosis; hepatic steatosis; hepatitis; liver disease; microbiome; non-invasive.

MeSH terms

  • Adult
  • Aged
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / microbiology*
  • Male
  • Metagenomics / methods
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / microbiology*
  • Prognosis
  • Prospective Studies