Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, USA.
Hepatology. 2024 Aug 1;80(2):465-485. doi: 10.1097/HEP.0000000000000344. Epub 2023 Mar 6.
Cirrhosis is characterized by inflammation, degeneration, and fibrosis of liver tissue. Along with being the most common cause of liver failure and liver transplant, cirrhosis is a significant risk factor for several neuropsychiatric conditions. The most common of these is HE, which is characterized by cognitive and ataxic symptoms, resulting from the buildup of metabolic toxins with liver failure. However, cirrhosis patients also show a significantly increased risk for neurodegenerative diseases such as Alzheimer and Parkinson diseases, and for mood disorders such as anxiety and depression. In recent years, more attention has been played to communication between the ways the gut and liver communicate with each other and with the central nervous system, and the way these organs influence each other's function. This bidirectional communication has come to be known as the gut-liver-brain axis. The gut microbiome has emerged as a key mechanism affecting gut-liver, gut-brain, and brain-liver communication. Clinical studies and animal models have demonstrated the significant patterns of gut dysbiosis when cirrhosis is present, both with or without concomitant alcohol use disorder, and have provided compelling evidence that this dysbiosis also influences the cognitive and mood-related behaviors. In this review, we have summarized the pathophysiological and cognitive effects associated with cirrhosis, links to cirrhosis-associated disruption of the gut microbiome, and the current evidence from clinical and preclinical studies for the modulation of the gut microbiome as a treatment for cirrhosis and associated neuropsychiatric conditions.
肝硬化的特征是肝脏组织的炎症、变性和纤维化。肝硬化是肝衰竭和肝移植的最常见原因,也是几种神经精神疾病的重要危险因素。其中最常见的是肝性脑病(HE),其特征是认知和共济失调症状,是由于肝功能衰竭导致代谢毒素堆积所致。然而,肝硬化患者也显著增加了患阿尔茨海默病和帕金森病等神经退行性疾病以及焦虑和抑郁等情绪障碍的风险。近年来,人们越来越关注肠道与肝脏之间的相互交流方式以及它们与中枢神经系统之间的相互交流方式,以及这些器官如何影响彼此的功能。这种双向交流被称为肠-肝-脑轴。肠道微生物组已成为影响肠-肝、肠-脑和脑-肝通讯的关键机制。临床研究和动物模型表明,肝硬化存在时,无论是否伴有酒精使用障碍,都会出现明显的肠道菌群失调模式,并提供了令人信服的证据表明,这种菌群失调也会影响认知和与情绪相关的行为。在这篇综述中,我们总结了与肝硬化相关的病理生理和认知影响、与肝硬化相关的肠道微生物组紊乱的联系,以及临床和临床前研究中关于调节肠道微生物组作为治疗肝硬化和相关神经精神疾病的证据。