Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Front Immunol. 2023 Apr 14;14:1139554. doi: 10.3389/fimmu.2023.1139554. eCollection 2023.
Cirrhosis is the common end-stage of chronic liver diseases of different etiology. The altered bile acids metabolism in the cirrhotic liver and the increase in the blood-brain barrier permeability, along with the progressive dysbiosis of intestinal microbiota, contribute to gut immunity changes, from compromised antimicrobial host defense to pro-inflammatory adaptive responses. In turn, these changes elicit a disruption in the epithelial and gut vascular barriers, promoting the increased access of potential pathogenic microbial antigens to portal circulation, further aggravating liver disease. After summarizing the key aspects of gut immunity during homeostasis, this review is intended to update the contribution of liver and brain metabolites in shaping the intestinal immune status and, in turn, to understand how the loss of homeostasis in the gut-associated lymphoid tissue, as present in cirrhosis, cooperates in the advanced chronic liver disease progression. Finally, several therapeutic approaches targeting the intestinal homeostasis in cirrhosis are discussed.
肝硬化是不同病因引起的慢性肝病的共同终末期。肝硬化时胆汁酸代谢改变,血脑屏障通透性增加,同时肠道微生物群失调逐渐加重,导致肠道免疫改变,从抗菌宿主防御受损到促炎适应性反应。反过来,这些变化破坏了上皮细胞和肠道血管屏障,促进潜在致病性微生物抗原进入门静脉循环,进一步加重肝脏疾病。在总结了稳态时肠道免疫的关键方面后,本综述旨在更新肝脏和大脑代谢物在塑造肠道免疫状态方面的作用,并进一步了解肝硬化时肠道相关淋巴组织稳态丧失如何协同进展性慢性肝病的发生。最后,讨论了几种针对肝硬化肠道稳态的治疗方法。