1. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease
- Author
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Cyrielle Caussy, Claude B. Sirlin, J. Craig Venter, Niels Klitgord, Rohit Loomba, Richele Bettencourt, Marcus B. Jones, Karen E. Nelson, Parambir S. Dulai, Victor Seguritan, Chi-Hua Chen, David A. Brenner, Lauren M. Brinkac, Bernd Schnabl, Archana Bhatt, Tao Long, Sarah K. Highlander, Weizhong Li, William H. Biggs, Shibu Yooseph, Nicholas J. Schork, CFD Lab [Montréal], Department of Mechanical Engineering [Montréal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), UC San Diego NAFLD Research Center, UC San Diego School of Medicine, Dept Anim Ind, Livestock Ind Sect, Council of agriculture, Department of Medicine, University of California [San Diego] (UC San Diego), University of California-University of California, Celera Genomics (CRA), Celera Genomics, McGill University-McGill University, Institut National de la Recherche Agronomique (INRA)-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), and Department of Oceanography and Fisheries
- Subjects
Liver Cirrhosis ,Male ,0301 basic medicine ,Pathology ,Cirrhosis ,Physiology ,[SDV]Life Sciences [q-bio] ,microbiome ,Medical Biochemistry and Metabolomics ,Gastroenterology ,Oral and gastrointestinal ,Hepatitis ,Feces ,Liver disease ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Nonalcoholic fatty liver disease ,Prospective Studies ,0303 health sciences ,hepatic steatosis ,Liver Disease ,Fatty liver ,NASH ,Middle Aged ,Prognosis ,3. Good health ,biomarker ,Biomarker (medicine) ,Female ,030211 gastroenterology & hepatology ,Adult ,medicine.medical_specialty ,non-invasive ,Chronic Liver Disease and Cirrhosis ,digestive system ,Article ,Endocrinology & Metabolism ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,Microbiome ,Molecular Biology ,030304 developmental biology ,Aged ,fatty liver ,Bacteria ,business.industry ,cirrhosis ,fibrosis ,Human Genome ,Cell Biology ,medicine.disease ,Gastrointestinal Microbiome ,Good Health and Well Being ,030104 developmental biology ,Dysbiosis ,Metagenomics ,Biochemistry and Cell Biology ,Digestive Diseases ,business - 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 characterizedthe 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 or4fibrosis). 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 diagnosticaccuracy (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.
- Published
- 2019
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