Sung Hotaik, Kim Seung Woo, Hong Meegun, Suk Ki Tae
Hotaik Sung, Department of Molecular and Cell Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
World J Gastroenterol. 2016 Aug 7;22(29):6673-82. doi: 10.3748/wjg.v22.i29.6673.
Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.
肠道微生物群在酒精性肝病(ALD)的发病机制中起关键作用。饮酒会导致肠道通透性增加、小肠细菌过度生长和肠道生态失调。这些因素促使微生物产物通过门静脉系统向肝脏的转运增加。随后,诸如脂多糖之类的细菌内毒素与Toll样受体4信号通路相关联,在肝脏环境中引发一系列有害的免疫反应。由于有害炎症与ALD诱导的微生物群失衡之间存在密切关联,因此在治疗酒精性患者时应考虑采取旨在重建肠道稳态的治疗方法。为此,一些关于益生菌的初步研究证实了它们在抑制促炎细胞因子和改善ALD患者肝功能方面的有效性。此外,将益生元与抗生素的使用与减轻酒精性肝损伤联系起来的研究很少。鉴于这些初步结果很有前景,有必要开展大规模随机研究,以阐明这些基于微生物群的治疗方法对肠道菌群和相关免疫反应的影响,同时还要探讨有关最佳给药方式的问题。最后,粪便微生物群移植已被证明是调节肠道微生物群的有效方法,作为ALD的一种潜在治疗选择值得进一步研究。