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

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 Jackson, John O’Sullivan, Martin Weltman, Geoffrey McCaughan, Emad El-Omar and Amany Zekry ()
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Jason Behary: University of New South Wales
Nadia Amorim: University of New South Wales
Xiao-Tao Jiang: University of New South Wales
Anita Raposo: University of New South Wales
Lan Gong: University of New South Wales
Emily McGovern: 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
John O’Sullivan: University of Sydney
Martin Weltman: Nepean Hospital
Geoffrey McCaughan: Royal Prince Alfred Hospital
Emad El-Omar: University of New South Wales
Amany Zekry: University of New South Wales

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20422-7

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