Giraud Julie, Saleh Maya
ImmunoConcEpT, CNRS, UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
Department of Medicine, McGill University, Montreal, QC H3G 0B1, Canada.
Cancers (Basel). 2021 Aug 27;13(17):4342. doi: 10.3390/cancers13174342.
Hepatocellular carcinoma (HCC) is a classical inflammation-promoted cancer that occurs in a setting of liver diseases, including nonalcoholic fatty liver disease (NAFLD) or alcoholic liver disease (ALD). These pathologies share key characteristics, notably intestinal dysbiosis, increased intestinal permeability and an imbalance in bile acids, choline, fatty acids and ethanol metabolites. Translocation of microbial- and danger-associated molecular patterns (MAMPs and DAMPs) from the gut to the liver elicits profound chronic inflammation, leading to severe hepatic injury and eventually HCC progression. In this review, we first describe how the gut and the liver communicate and discuss mechanisms by which the intestinal microbiota elicit hepatic inflammation and HCC. We focus on the role of microbial products, e.g., MAMPs, host inflammatory effectors and host-microbiome-derived metabolites in tumor-promoting mechanisms, including cell death and senescence. Last, we explore the potential of harnessing the microbiota to treat liver diseases and HCC.
肝细胞癌（HCC）是一种典型的炎症促进型癌症，发生于包括非酒精性脂肪性肝病（NAFLD）或酒精性肝病（ALD）在内的肝脏疾病背景下。这些病症具有关键的共同特征，尤其是肠道微生物群失调、肠道通透性增加以及胆汁酸、胆碱、脂肪酸和乙醇代谢产物失衡。微生物相关分子模式（MAMPs）和危险相关分子模式（DAMPs）从肠道向肝脏的易位引发严重的慢性炎症，导致严重肝损伤并最终促使HCC进展。在本综述中，我们首先描述肠道与肝脏如何相互作用，并讨论肠道微生物群引发肝脏炎症和HCC的机制。我们重点关注微生物产物（如MAMPs）、宿主炎症效应物以及宿主-微生物群衍生代谢产物在包括细胞死亡和衰老在内的肿瘤促进机制中的作用。最后，我们探讨利用微生物群治疗肝脏疾病和HCC的潜力。
