Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD

Giljae Lee, Hyun Ju You, Jasmohan S. Bajaj, Sae Kyung Joo, Junsun Yu, Seoyeon Park, Hyena Kang, Jeong Hwan Park, Jung Ho Kim, Dong Hyeon Lee, Seonhwa Lee, Won Kim () and GwangPyo Ko ()
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Giljae Lee: Seoul National University
Hyun Ju You: Seoul National University
Jasmohan S. Bajaj: Virginia Commonwealth University and McGuire VA Medical Center
Sae Kyung Joo: Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center
Junsun Yu: Seoul National University
Seoyeon Park: Seoul National University
Hyena Kang: Seoul National University
Jeong Hwan Park: Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center
Jung Ho Kim: Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center
Dong Hyeon Lee: Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center
Seonhwa Lee: Korea University
Won Kim: Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center
GwangPyo Ko: Seoul National University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18754-5

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