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

Author

Listed:
  • Giljae Lee

    (Seoul National University)

  • Hyun Ju You

    (Seoul National University
    Seoul National University
    Center for Human and Environmental Microbiome, Institute of Health and Environment, 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
    Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University
    KoBioLabs, Inc.
    Bio-MAX/N-Bio, Seoul National University)

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.

Suggested Citation

  • 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 & GwangPyo Ko, 2020. "Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18754-5
    DOI: 10.1038/s41467-020-18754-5
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    Cited by:

    1. Runtan Cheng & Lu Wang & Shenglong Le & Yifan Yang & Can Zhao & Xiangqi Zhang & Xin Yang & Ting Xu & Leiting Xu & Petri Wiklund & Jun Ge & Dajiang Lu & Chenhong Zhang & Luonan Chen & Sulin Cheng, 2022. "A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Yumeng Peng & Qiang Zeng & Luming Wan & Enhao Ma & Huilong Li & Xiaopan Yang & Yanhong Zhang & Linfei Huang & Haotian Lin & Jiangyue Feng & Yixin Xu & Jingfei Li & Muyi Liu & Jing Liu & Changqin Lin &, 2021. "GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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