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

Cyrielle Caussy; Anupriya Tripathi; Greg Humphrey; Shirin Bassirian; Seema Singh; Claire Faulkner; Ricki Bettencourt; Emily Rizo; Lisa Richards; Zhenjiang Z Xu; Michael R Downes; Ronald M Evans; David A Brenner; Claude B Sirlin; Rob Knight; Rohit Loomba

doi:10.1038/s41467-019-09455-9

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

Nat Commun. 2019 Mar 29;10(1):1406. doi: 10.1038/s41467-019-09455-9.

Authors

Cyrielle Caussy^{1

2}, Anupriya Tripathi^{3

4

5

6}, Greg Humphrey⁴, Shirin Bassirian¹, Seema Singh¹, Claire Faulkner¹, Ricki Bettencourt^{1

7}, Emily Rizo¹, Lisa Richards¹, Zhenjiang Z Xu⁴, Michael R Downes⁸, Ronald M Evans⁸, David A Brenner^{1

9}, Claude B Sirlin¹⁰, Rob Knight^{3

4

11

12}, Rohit Loomba^{13

14

15}

Affiliations

¹ NAFLD Research Center, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
² Université Lyon 1, Hospices Civils de Lyon, Lyon, 69002, France.
³ Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, 92093, USA.
⁴ Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.
⁵ Division of Biological Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
⁶ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 93093, USA.
⁷ Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
⁸ Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
⁹ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
¹⁰ Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, 92037, USA.
¹¹ Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, 92093, USA.
¹² Department of BioEngineering, University of California San Diego, La Jolla, CA, 92093, USA.
¹³ NAFLD Research Center, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. [email protected].
¹⁴ Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, 92093, USA. [email protected].
¹⁵ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Bacteria / classification
Family
Feces / microbiology
Female
Gastrointestinal Microbiome*
Humans
Liver Cirrhosis / microbiology*
Male
Non-alcoholic Fatty Liver Disease / microbiology*
ROC Curve

Abstract

Publication types

MeSH terms

Grants and funding