Author information
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. roloomba@ucsd.edu.
14 Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, 92093, USA. roloomba@ucsd.edu.
15 Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. roloomba@ucsd.edu.
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.