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

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

Author information

1
NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: roloomba@ucsd.edu.
2
Human Longevity, San Diego, CA 92121, USA.
3
Human Longevity, San Diego, CA 92121, USA; J. Craig Venter Institute, La Jolla, CA 92037, USA.
4
NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5
NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
6
J. Craig Venter Institute, La Jolla, CA 92037, USA.
7
Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
8
J. Craig Venter Institute, Rockville, MD 20850, USA.

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.

KEYWORDS:

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

PMID:
28467925
PMCID:
PMC5502730
DOI:
10.1016/j.cmet.2017.04.001
[Indexed for MEDLINE]
Free PMC Article

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