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A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease

Author

Listed:
  • Cyrielle Caussy

    (University of California San Diego
    Hospices Civils de Lyon)

  • Anupriya Tripathi

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Greg Humphrey

    (University of California San Diego)

  • Shirin Bassirian

    (University of California San Diego)

  • Seema Singh

    (University of California San Diego)

  • Claire Faulkner

    (University of California San Diego)

  • Ricki Bettencourt

    (University of California San Diego
    University of California San Diego)

  • Emily Rizo

    (University of California San Diego)

  • Lisa Richards

    (University of California San Diego)

  • Zhenjiang Z. Xu

    (University of California San Diego)

  • Michael R. Downes

    (Salk Institute for Biological Studies)

  • Ronald M. Evans

    (Salk Institute for Biological Studies)

  • David A. Brenner

    (University of California San Diego
    University of California San Diego)

  • Claude B. Sirlin

    (University of California at San Diego)

  • Rob Knight

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Rohit Loomba

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

Abstract

The presence of cirrhosis in nonalcoholic-fatty-liver-disease (NAFLD) is the most important predictor of liver-related mortality. Limited data exist concerning the diagnostic accuracy of gut-microbiome-derived signatures for detecting NAFLD-cirrhosis. Here we report 16S gut-microbiome compositions of 203 uniquely well-characterized participants from a prospective twin and family cohort, including 98 probands encompassing the entire spectrum of NAFLD and 105 of their first-degree relatives, assessed by advanced magnetic-resonance-imaging. We show strong familial correlation of gut-microbiome profiles, driven by shared housing. We report a panel of 30 features, including 27 bacterial features with discriminatory ability to detect NAFLD-cirrhosis using a Random Forest classifier model. In a derivation cohort of probands, the model has a robust diagnostic accuracy (AUROC of 0.92) for detecting NAFLD-cirrhosis, confirmed in a validation cohort of relatives of proband with NAFLD-cirrhosis (AUROC of 0.87). This study provides evidence for a fecal-microbiome-derived signature to detect NAFLD-cirrhosis.

Suggested Citation

  • Cyrielle Caussy & Anupriya Tripathi & Greg Humphrey & Shirin Bassirian & Seema Singh & Claire Faulkner & Ricki Bettencourt & Emily Rizo & Lisa Richards & Zhenjiang Z. Xu & Michael R. Downes & Ronald M, 2019. "A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09455-9
    DOI: 10.1038/s41467-019-09455-9
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    Cited by:

    1. Kai Markus Schneider & Antje Mohs & Wenfang Gui & Eric J. C. Galvez & Lena Susanna Candels & Lisa Hoenicke & Uthayakumar Muthukumarasamy & Christian H. Holland & Carsten Elfers & Konrad Kilic & Caroli, 2022. "Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Giulia Angelini & Lidia Castagneto-Gissey & Serenella Salinari & Alessandro Bertuzzi & Danila Anello & Meenakshi Pradhan & Marlen Zschätzsch & Paul Ritter & Carel W. Le Roux & Francesco Rubino & Nicol, 2022. "Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Ming Yang & Xiaoqiang Qi & Nan Li & Jussuf T. Kaifi & Shiyou Chen & Andrew A. Wheeler & Eric T. Kimchi & Aaron C. Ericsson & R. Scott Rector & Kevin F. Staveley-O’Carroll & Guangfu Li, 2023. "Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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