1. A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis
- Author
-
Oh, T. G., Kim, S. M., Caussy, C., Fu, T., Guo, J., Bassirian, S., Singh, S., Madamba, E. V., Bettencourt, R., Richards, L., Raffatellu, M., Dorrestein, P. C., Yu, R. T., Atkins, A. R., Huan, T., Brenner, D. A., Sirlin, C. B., Knight, R., Downes, M., Evans, R. M., Loomba, R., Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), EDF Energy R&D UK Centre, EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), UC San Diego NAFLD Research Center, UC San Diego School of Medicine, Department of Medicine, University of California [San Diego] (UC San Diego), University of California-University of California, University of California, CarMeN, laboratoire, The Salk Institute for Biological Studies, University of California (UC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Computer Science [Vancouver] (UBC Computer Science), and University of British Columbia (UBC)
- Subjects
0301 basic medicine ,Liver Cirrhosis ,Male ,Cirrhosis ,Physiology ,[SDV]Life Sciences [q-bio] ,microbiome ,Disease ,Medical Biochemistry and Metabolomics ,Oral and gastrointestinal ,Hepatitis ,Cohort Studies ,Feces ,0302 clinical medicine ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,80 and over ,2.1 Biological and endogenous factors ,Aetiology ,10. No inequality ,ComputingMilieux_MISCELLANEOUS ,liver fibrosis ,0303 health sciences ,Nafld ,Liver Disease ,Fatty liver ,NASH ,Middle Aged ,metabolomics ,[SDV] Life Sciences [q-bio] ,Metabolome ,biomarker ,030211 gastroenterology & hepatology ,Female ,non-alcoholic steatohepatitis ,Human ,Adult ,Chronic Liver Disease and Cirrhosis ,Nash ,Biology ,Article ,03 medical and health sciences ,Endocrinology & Metabolism ,Metabolomics ,Clinical Research ,NAFLD ,medicine ,Genetics ,microbiota ,Humans ,Microbiome ,Aspartate Aminotransferases ,Molecular Biology ,Serum Albumin ,030304 developmental biology ,Aged ,fatty liver ,metagenomics ,cirrhosis ,Human Genome ,non-alcoholic fatty liver disease ,Cell Biology ,medicine.disease ,Biomarker (cell) ,Gastrointestinal Microbiome ,030104 developmental biology ,Metagenomics ,Immunology ,Metagenome ,Biochemistry and Cell Biology ,Digestive Diseases ,030217 neurology & neurosurgery - Abstract
Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, area under curve [AUC]). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species might offer universal utility as a non-invasive diagnostic test for cirrhosis.
- Published
- 2020
- Full Text
- View/download PDF