Malaguarnera Giulia, Giordano Maria, Nunnari Giuseppe, Bertino Gaetano, Malaguarnera Michele
Giulia Malaguarnera, Michele Malaguarnera, Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, 95100 Catania, Italy.
World J Gastroenterol. 2014 Nov 28;20(44):16639-48. doi: 10.3748/wjg.v20.i44.16639.
Alcoholic liver disease (ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.
酒精性肝病（ALD）是许多西方国家肝硬化最常见的病因，其发病率和死亡率都很高。发病机制的特点是酒精代谢中间产物之间存在复杂的相互作用。肠道细菌菌群自身可通过碳水化合物发酵产生内源性乙醇。酒精的肠道代谢会产生高浓度的有毒乙醛，这会改变肠道通透性和微生物群平衡。此外，它还会导致肝细胞直接损伤。长期饮酒的患者肠道微生物群会发生改变，尤其是革兰氏阴性菌数量增加。这会导致内毒素血症和免疫系统过度激活。内毒素是革兰氏阴性菌细胞壁的组成成分。库普弗细胞上存在的两种受体，即分化抗原簇14和Toll样受体4，可识别内毒素。多项研究已证明肠-肝轴的重要性，近年来人们研究了新的治疗方法，以通过改变肠道微生物群来减缓ALD的进展。这已将注意力集中在抗生素、益生元、益生菌和合生元上。
