Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Recently, increasing investigation of the microbiome–gut–liver axis enhances our understanding of the role of the gut microbiota in promoting the progression of liver disease and the development of HCC. In this review, we summarize mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on bacterial dysbiosis, the leaky gut, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. Furthermore, we discuss the important potential of gut microbiota as an early diagnostic biomarker of HCC. Gut microbiota may be as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We outlook in detail therapeutic modalities in which targeting the gut microbiota for the prevention of disease progression and HCC development seems promising.


中文翻译：

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肠道微生物组和肝细胞癌：早期诊断生物标志物和新疗法的意义

肝细胞癌（HCC）是全球癌症死亡的第三大原因。HCC 几乎完全发生在慢性肝病患者身上，由通常跨越数十年的肝损伤、炎症和再生的恶性循环驱动。最近，对微生物组-肠道-肝轴的研究不断增加，加深了我们对肠道菌群在促进肝病进展和 HCC 发展中的作用的理解。在这篇综述中，我们总结了肠道微生物群促进肝癌发生的机制，重点关注细菌生态失调、肠道渗漏、微生物相关分子模式和细菌代谢物作为驱动癌症促进肝脏炎症、纤维化和遗传毒性的关键途径。此外，我们讨论了肠道微生物群作为 HCC 早期诊断生物标志物的重要潜力。肠道微生物群可能是同时预防晚期肝病患者慢性肝病进展和HCC发展的有希望的靶点。我们详细展望了针对肠道微生物群以预防疾病进展和 HCC 发展的治疗方式似乎很有希望。