Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, Unversité Catholique de Louvain, 1200 Brussels, Belgium.
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Int J Mol Sci. 2021 Nov 24;22(23):12687. doi: 10.3390/ijms222312687.
Chronic alcohol consumption and alcohol-associated liver disease (ALD) represent a major public health problem worldwide. Only a minority of patients with an alcohol-use disorder (AUD) develop severe forms of liver disease (e.g., steatohepatitis and fibrosis) and finally progress to the more advanced stages of ALD, such as severe alcohol-associated hepatitis and decompensated cirrhosis. Emerging evidence suggests that gut barrier dysfunction is multifactorial, implicating microbiota changes, alterations in the intestinal epithelium, and immune dysfunction. This failing gut barrier ultimately allows microbial antigens, microbes, and metabolites to translocate to the liver and into systemic circulation. Subsequent activation of immune and inflammatory responses contributes to liver disease progression. Here we review the literature about the disturbance of the different host defense mechanisms linked to gut barrier dysfunction, increased microbial translocation, and impairment of liver and systemic inflammatory responses in the different stages of ALD.
慢性酒精消费和与酒精相关的肝病 (ALD) 是全球范围内的一个主要公共卫生问题。只有少数患有酒精使用障碍 (AUD) 的患者会发展为严重的肝病（如脂肪性肝炎和纤维化），最终进展为更严重的 ALD 阶段，如严重的酒精性肝炎和失代偿性肝硬化。新出现的证据表明，肠道屏障功能障碍是多因素的，涉及微生物群的变化、肠道上皮的改变和免疫功能障碍。这种肠道屏障的失效最终允许微生物抗原、微生物和代谢物转移到肝脏和全身循环中。随后的免疫和炎症反应的激活导致肝脏疾病的进展。在这里，我们回顾了关于不同宿主防御机制的文献，这些机制与肠道屏障功能障碍、微生物易位增加以及 ALD 不同阶段肝脏和全身炎症反应受损有关。
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