Yang Ming, Khoukaz Lea, Qi Xiaoqiang, Kimchi Eric T, Staveley-O'Carroll Kevin F, Li Guangfu
Department of Surgery, University of Missouri, Columbia, MO 65212, USA.
Harry S. Truman Memorial VA Hospital, Columbia, MO 65201, USA.
Biomedicines. 2021 Dec 13;9(12):1893. doi: 10.3390/biomedicines9121893.
Nonalcoholic fatty liver disease (NAFLD) with pathogenesis ranging from nonalcoholic fatty liver (NAFL) to the advanced form of nonalcoholic steatohepatitis (NASH) affects about 25% of the global population. NAFLD is a chronic liver disease associated with obesity, type 2 diabetes, and metabolic syndrome, which is the most increasing factor that causes hepatocellular carcinoma (HCC). Although advanced progress has been made in exploring the pathogenesis of NAFLD and penitential therapeutic targets, no therapeutic agent has been approved by Food and Drug Administration (FDA) in the United States. Gut microbiota-derived components and metabolites play pivotal roles in shaping intrahepatic immunity during the progression of NAFLD or NASH. With the advance of techniques, such as single-cell RNA sequencing (scRNA-seq), each subtype of immune cells in the liver has been studied to explore their roles in the pathogenesis of NAFLD. In addition, new molecules involved in gut microbiota-mediated effects on NAFLD are found. Based on these findings, we first summarized the interaction of diet-gut microbiota-derived metabolites and activation of intrahepatic immunity during NAFLD development and progression. Treatment options by targeting gut microbiota and important molecular signaling pathways are then discussed. Finally, undergoing clinical trials are selected to present the potential application of treatments against NAFLD or NASH.
非酒精性脂肪性肝病（NAFLD）的发病机制涵盖从非酒精性脂肪肝（NAFL）到晚期非酒精性脂肪性肝炎（NASH），影响着全球约25%的人口。NAFLD是一种与肥胖、2型糖尿病和代谢综合征相关的慢性肝病，是导致肝细胞癌（HCC）的最主要增长因素。尽管在探索NAFLD的发病机制和潜在治疗靶点方面已经取得了显著进展，但在美国，尚无治疗药物获得食品药品监督管理局（FDA）的批准。肠道微生物群衍生的成分和代谢产物在NAFLD或NASH进展过程中塑造肝内免疫方面发挥着关键作用。随着技术的进步，如单细胞RNA测序（scRNA-seq），肝脏中每种免疫细胞亚型都已得到研究，以探索它们在NAFLD发病机制中的作用。此外，还发现了参与肠道微生物群介导的对NAFLD影响的新分子。基于这些发现，我们首先总结了在NAFLD发生和发展过程中饮食-肠道微生物群衍生代谢产物与肝内免疫激活之间的相互作用。然后讨论了针对肠道微生物群和重要分子信号通路的治疗选择。最后，挑选正在进行的临床试验来展示针对NAFLD或NASH治疗的潜在应用。
