한빛사 논문
Giljae Lee1,10, Hyun Ju You1,2,3,10, Jasmohan S. Bajaj4, Sae Kyung Joo5, Junsun Yu1, Seoyeon Park1, Hyena Kang1, Jeong Hwan Park6, Jung Ho Kim6, Dong Hyeon Lee5, Seonhwa Lee7, Won Kim5,* & GwangPyo Ko1,3,8,9,*
1Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
2Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea.
3Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea.
4Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA 23249, USA.
5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea.
6Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea.
7Department of Bio-convergence Engineering, Korea University, Seoul 02841, Republic of Korea.
8KoBioLabs, Inc., Seoul 08826, Republic of Korea.
9Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Republic of Korea.
10These authors contributed equally: Giljae Lee, Hyun Ju You.
*Corresponding author
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.
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