1. Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD
- Author
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Jung Ho Kim, H.R. Kang, Sae Kyung Joo, Hyun Ju You, Won Kim, Dong Hyeon Lee, Giljae Lee, Seoyeon Park, Junsun Yu, Jasmohan S. Bajaj, Jeong Hwan Park, GwangPyo Ko, and Seon Hwa Lee
- Subjects
0301 basic medicine ,Liver Cirrhosis ,General Physics and Astronomy ,Gastroenterology ,Pathogenesis ,Feces ,Mice ,0302 clinical medicine ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,RNA, Ribosomal, 16S ,Nonalcoholic fatty liver disease ,lcsh:Science ,Multidisciplinary ,Cohort ,030211 gastroenterology & hepatology ,Ruminococcaceae ,medicine.medical_specialty ,Science ,Liver fibrosis ,Veillonellaceae ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Article ,Bile Acids and Salts ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Microbiome ,Obesity ,Bacteria ,business.industry ,nutritional and metabolic diseases ,Reproducibility of Results ,Diagnostic markers ,General Chemistry ,medicine.disease ,digestive system diseases ,Gastrointestinal Microbiome ,030104 developmental biology ,lcsh:Q ,Propionates ,business ,Biomarkers - 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.
- Published
- 2020