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Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.
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1 Seoul National University, Department of Environmental Health Sciences, Graduate School of Public Health, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
2 Seoul National University, Department of Environmental Health Sciences, Graduate School of Public Health, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Institute of Health and Environment, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
3 Virginia Commonwealth University and McGuire VA Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Richmond, USA (GRID:grid.413640.4) (ISNI:0000 0004 0420 6241)
4 Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
5 Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Department of Pathology, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
6 Korea University, Department of Bio-convergence Engineering, Seoul, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678)
7 Seoul National University, Department of Environmental Health Sciences, Graduate School of Public Health, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); KoBioLabs, Inc., Seoul, Republic of Korea (GRID:grid.31501.36); Bio-MAX/N-Bio, Seoul National University, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)