St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
Nat Commun. 2021 Jan 8;12(1):187. doi: 10.1038/s41467-020-20422-7.
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.
肠道微生物群被报道可调节肝细胞癌 (HCC) 中的免疫反应。在这里，我们采用宏基因组学和代谢组学研究来描述非酒精性脂肪性肝病 (NAFLD) 相关肝硬化患者、伴有或不伴有 HCC 的肠道微生物群，并在体外模型中评估其对外周免疫反应的影响。我们发现，肠道微生物群的失调是 NAFLD 肝硬化患者的特征，随着 HCC 的发展，其组成和功能发生变化。NAFLD-HCC 患者的微生物群的基因功能支持短链脂肪酸的产生，这通过代谢组学研究得到了证实。体外研究表明，来自 NAFLD-HCC 微生物群的细菌提取物，但不是来自对照组的提取物，可引起 T 细胞免疫抑制表型，其特征是调节性 T 细胞的扩增和 CD8+T 细胞的衰减。我们的研究表明，NAFLD-HCC 中的肠道微生物群具有独特的微生物组/代谢组特征，并能调节外周免疫反应。
