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Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma

Author

Listed:
  • Jason Behary

    (University of New South Wales
    University of New South Wales
    St George Hospital)

  • Nadia Amorim

    (University of New South Wales
    University of New South Wales)

  • Xiao-Tao Jiang

    (University of New South Wales
    University of New South Wales)

  • Anita Raposo

    (University of New South Wales
    University of New South Wales)

  • Lan Gong

    (University of New South Wales
    University of New South Wales)

  • Emily McGovern

    (University of New South Wales
    University of New South Wales)

  • Ragy Ibrahim

    (St George Hospital)

  • Francis Chu

    (St George Hospital)

  • Carlie Stephens

    (St George Hospital)

  • Hazem Jebeili

    (St George Hospital)

  • Vincenzo Fragomeli

    (Nepean Hospital)

  • Yen Chin Koay

    (University of Sydney)

  • Miriam Jackson

    (University of New South Wales
    University of New South Wales)

  • John O’Sullivan

    (University of Sydney)

  • Martin Weltman

    (Nepean Hospital)

  • Geoffrey McCaughan

    (Royal Prince Alfred Hospital
    Royal Prince Alfred Hospital)

  • Emad El-Omar

    (University of New South Wales
    University of New South Wales
    St George Hospital)

  • Amany Zekry

    (University of New South Wales
    University of New South Wales
    St George Hospital)

Abstract

The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.

Suggested Citation

  • Jason Behary & Nadia Amorim & Xiao-Tao Jiang & Anita Raposo & Lan Gong & Emily McGovern & Ragy Ibrahim & Francis Chu & Carlie Stephens & Hazem Jebeili & Vincenzo Fragomeli & Yen Chin Koay & Miriam Jac, 2021. "Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20422-7
    DOI: 10.1038/s41467-020-20422-7
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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.

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