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

Rohit Loomba*, Victor Seguritan, Weizhong Li, Tao Long, Niels Klitgord, Archana Bhatt, Parambir Singh Dulai, Cyrielle Caussy, Richele Bettencourt, Sarah K. Highlander, Marcus B. Jones, Claude B. Sirlin, Bernd Schnabl, Lauren Brinkac, Nicholas Schork, Chi Hua Chen, David A. Brenner, William Biggs, Shibu Yooseph, J. Craig VenterKaren E. Nelson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

417 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1054-1062.e5
JournalCell Metabolism
Volume25
Issue number5
DOIs
StatePublished - May 2 2017
Externally publishedYes

Keywords

  • biomarker
  • cirrhosis
  • fatty liver
  • fibrosis
  • hepatic steatosis
  • hepatitis
  • liver disease
  • microbiome
  • NASH
  • non-invasive

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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