Fuenzalida Catalina, Dufeu María Soledad, Poniachik Jaime, Roblero Juan Pablo, Valenzuela-Pérez Lucía, Beltrán Caroll Jenny
Laboratory of Inmunogastroenterology, Gastroenterology Unit, Medicine Department, Hospital Clínico Universidad de Chile, Santiago, Chile.
Medicine Faculty, Universidad de Chile, Santiago, Chile.
Front Pharmacol. 2021 Sep 24;12:729950. doi: 10.3389/fphar.2021.729950. eCollection 2021.
Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer's, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.
酒精性肝病（ALD）是全球范围内患有酒精使用障碍（AUD）的成年人发病的主要原因之一。其临床病程从脂肪变性到酒精性肝炎，进而发展为更严重的肝损伤形式，如肝硬化和肝细胞癌。ALD的发病机制复杂，其发展涉及多种因素，包括环境因素、遗传易感性、免疫反应以及肠-肝轴相互作用。长期饮酒会导致肠道微生物群的变化，这与肠道屏障功能的丧失和炎症反应有关，而炎症反应会加剧酒精引发的肝损伤进展。酒精代谢产物如乙醛、脂质过氧化衍生的醛丙二醛（MDA）和蛋白质加合物作为损害肝脏的肝毒素，并加剧全身炎症。此外，乙醇通过血脑屏障（BBB）对中枢神经系统（CNS）造成直接损害，引发氧化应激，导致神经炎症。总体而言，这些过程与ALD患者易患抑郁症、焦虑症和酒精渴望有关。最近的证据表明，益生菌可以逆转酒精引起的微生物群变化，并通过恢复肠道微生物组成来预防ALD的进展。然而，益生菌对饮酒行为的影响尚未得到充分研究。益生菌已被用于通过恢复微生物群和减少全身及CNS炎症来治疗各种疾病。一些研究结果表明，益生菌可能改善阿尔茨海默病、自闭症谱系障碍患者的心理功能，并减弱吗啡镇痛耐受性。从这个意义上说，已经观察到肠道微生物群组成的改变以及使用益生菌对其进行调节会引起大脑中神经递质信号的变化，尤其是在多巴胺奖赏回路中。因此，不难想象，基于益生菌的ALD辅助治疗可能通过减少饮酒来降低疾病进展。本综述旨在介绍ALD中微生物群-肠-肝-脑轴潜在病理生理机制的最新进展，并提供证据支持使用益生菌作为辅助疗法来解决酒精使用障碍及其对肝损伤的影响。
