Discipline of Pediatrics, Department of Mother and Child Medicine, University of Medicine and Pharmacy, Grigore T. Popa, Iasi, Iasi, Romania.
Dig Liver Dis. 2013 Jul;45(7):543-51. doi: 10.1016/j.dld.2012.11.010. Epub 2012 Dec 29.
Non-alcoholic fatty liver disease is a multifactorial condition, ranging from simple steatosis to non-alcoholic steatohepatitis with or without fibrosis. In non-alcoholic fatty liver disease, alteration of gut microbiota and increased intestinal permeability increase exposure of the liver to gut-derived bacterial products: lipopolysaccharides and unmethylated CpG DNA. These products stimulate innate immune receptors, namely Toll-like receptors, which activate signalling pathways involved in liver inflammation and fibrogenesis. Currently, there are several studies on the involvement of lipopolysaccharide-activated Toll-like receptor 4 signalling in non-alcoholic fatty liver disease pathogenesis. There has been widespread interest in the study of the involvement of resident hepatic stellate cells and Kupffer cells activation in liver fibrogenesis upon TLR4 stimulation. Although the best evidence to support a role for gut microbiota in non-alcoholic fatty liver disease-induced fibrosis comes largely from animal models, data from human studies are accumulating and could lead to new therapeutic approaches. Therapeutic modulation of gut microflora may be an alternative strategy to develop an anti-fibrotic therapy. In this review, we discuss the relevant role of gut-liver axis in non-alcoholic liver disease-associated liver fibrosis and discuss the evidence on novel anti-fibrotic therapeutic approaches.
非酒精性脂肪性肝病是一种多因素疾病，其范围从单纯性脂肪变性到伴有或不伴有纤维化的非酒精性脂肪性肝炎。在非酒精性脂肪性肝病中，肠道微生物群的改变和肠道通透性的增加增加了肝脏对肠道来源的细菌产物（脂多糖和未甲基化 CpG DNA）的暴露。这些产物刺激先天免疫受体，即 Toll 样受体，从而激活参与肝脏炎症和纤维化的信号通路。目前，有几项关于脂多糖激活的 Toll 样受体 4 信号通路在非酒精性脂肪性肝病发病机制中的作用的研究。人们广泛关注 TLR4 刺激时驻留的肝星状细胞和枯否细胞激活在肝纤维化中的作用。尽管支持肠道微生物群在非酒精性脂肪性肝病诱导的纤维化中起作用的最佳证据主要来自动物模型，但来自人类研究的数据正在积累，并可能导致新的治疗方法。肠道微生物群的治疗性调节可能是开发抗纤维化治疗的一种替代策略。在这篇综述中，我们讨论了肠-肝轴在非酒精性肝病相关肝纤维化中的相关作用，并讨论了新型抗纤维化治疗方法的证据。
