Patel Sheena, Behara Rama, Swanson Garth R, Forsyth Christopher B, Voigt Robin M, Keshavarzian Ali
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA.
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
Biomolecules. 2015 Oct 15;5(4):2573-88. doi: 10.3390/biom5042573.
Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches.
酒精滥用是全球疾病负担的一个重要因素，可导致一部分酗酒者出现组织损伤和器官功能障碍。然而，一部分没有任何这些诱发因素的酗酒者也会发生酒精介导的器官损伤。胃肠道可能是酒精介导的器官损伤中炎症的一个重要来源。本综述的目的是评估酒精诱导内毒素血症的机制（包括微生物群失调和肠道通透性增加），并强调酒精诱导微生物群失调和肠道对内毒素通透性增加的诱发因素。包括免疫、物理和生化在内的屏障可调节毒素进入门静脉和体循环。此外，许多环境相互作用，包括那些受昼夜节律影响的相互作用，可影响酒精诱导的器官病理。似乎可以采取治疗措施，通过使肠道微生物群失调正常化和/或改善肠道屏障完整性来减轻酒精诱导的器官损伤。最终，驱动酒精性器官损伤进展的炎症过程似乎是多因素的。了解肠道在酒精性肝病发病机制中的作用可为致病和治疗方法提供进一步途径。
