Plaza-Díaz Julio, Solis-Urra Patricio, Aragón-Vela Jerónimo, Rodríguez-Rodríguez Fernando, Olivares-Arancibia Jorge, Álvarez-Mercado Ana I
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada.
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
Biomedicines. 2021 Feb 3;9(2):145. doi: 10.3390/biomedicines9020145.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).
非酒精性脂肪性肝病(NAFLD)是导致慢性肝病的一个日益常见的原因,与肥胖和代谢紊乱相关,如高血压、血脂异常或2型糖尿病。一种更严重的NAFLD类型,即非酒精性脂肪性肝炎(NASH),被认为是对全球健康的持续威胁,并显著增加了肝硬化、肝衰竭和肝细胞癌的风险。多项报告表明,肝脏脂肪变性与某些临床和生化标志物的升高有关,但预测潜力较低。此外,目前的成像方法在定量肝脏脂肪变性方面不准确且不充分,并且无法清晰区分微泡型和大泡型。另一方面,不健康状态通常表现为肠道微生物群改变,及其功能丧失。事实上,NAFLD的病理生理学与微生物多样性降低和肠道屏障减弱有关,使宿主暴露于细菌成分,并通过Toll样受体信号刺激免疫防御和炎症途径。此外,肝细胞中的这种炎症激活会促使单纯性脂肪变性发展为NASH。在本综述中,我们旨在:(a)总结关于人类和动物的研究,以确定肠道微生物群改变对NASH的影响;(b)评估这种改变作为该疾病预后和诊断生物标志物的潜在作用;以及(c)讨论微生物群在目前NAFLD/NASH治疗(即减肥手术、体育锻炼和生活方式、饮食、益生菌和益生元以及粪便微生物群移植)中的作用。