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.

Authors

Rohit Loomba¹, Victor Seguritan², Weizhong Li³, Tao Long², Niels Klitgord², Archana Bhatt⁴, Parambir Singh Dulai⁵, Cyrielle Caussy⁴, Richele Bettencourt⁴, Sarah K Highlander⁶, Marcus B Jones², Claude B Sirlin⁷, Bernd Schnabl⁵, Lauren Brinkac⁸, Nicholas Schork⁶, Chi-Hua Chen⁷, David A Brenner⁵, William Biggs², Shibu Yooseph³, J Craig Venter³, Karen E Nelson³

Affiliations

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.

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

Abstract

MeSH terms

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