Fukui Hiroshi
Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, 840 Shijo-cho Kashihara, 634-8522 Nara, Japan.
Microorganisms. 2015 Oct 28;3(4):759-91. doi: 10.3390/microorganisms3040759.
Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.
尽管给动物喂食酒精会使其肠道微生物发生明显变化，但只有部分酗酒者会出现明显的肠道生态失调，即拟杆菌门减少，变形菌门增加。肠道生态失调与酒精性肝病患者的肠道通透性增加和内毒素血症有关。酗酒者体内有益的乳酸杆菌和双歧杆菌数量也会进一步减少。大量从肠道转移的内毒素会强烈激活肝脏中的Toll样受体4，并在酒精性肝病（ALD）的进展中起重要作用，尤其是在严重酒精性肝损伤中。肠道微生物群和细菌内毒素还参与了非酒精性脂肪性肝病（NAFLD）及其向非酒精性脂肪性肝炎（NASH）进展的一些机制。有实验证据表明，高脂饮食会导致NAFLD出现特征性的生态失调，拟杆菌门减少，厚壁菌门和变形菌门增加，而且肠道生态失调本身可诱发肝脂肪变性和代谢综合征。临床数据支持上述生态失调情况，但具体细节存在差异。肠道生态失调和内毒素血症在主要并发症和预后方面对肝硬化患者有很大影响。针对生态失调的宏基因组学方法可能有助于分析NASH和肝硬化中紊乱的宿主代谢。对生态失调的管理可能会成为未来肝病治疗的基石。
