Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Medicine, University of California San Diego, San Diego, California, USA.
Gut. 2019 Feb;68(2):359-370. doi: 10.1136/gutjnl-2018-316307. Epub 2018 Aug 31.
The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.
非酒精性脂肪性肝病（NAFLD）的范围从常见于肥胖症的单纯性肝脂肪变性到非酒精性脂肪性肝炎不等，后者可进展为纤维化、肝硬化和肝细胞癌。NAFLD 的发病机制涉及环境、遗传和代谢因素，以及肠道微生物组及其产物的变化。肠道屏障功能障碍可促成 NAFLD 的发生和进展。尽管在评估人类肠道通透性方面存在技术限制，而且这些研究中的患者数量相对较少，但不到一半的患者存在肠道通透性增加和细菌产物易位。微生物衍生的代谢物及其影响的信号通路可能在 NAFLD 的发生中发挥更重要的作用。我们回顾了有助于 NAFLD 发生的微生物代谢物，如三甲胺、胆汁酸、短链脂肪酸和乙醇。我们讨论了微生物产生的代谢物可能影响疾病进展的机制，以及它们作为 NAFLD 的治疗靶点或生物标志物的潜在用途。
