利用肠道微生物组治疗失代偿性肝硬化和急性慢性肝功能衰

StephenW

Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure

    Jonel Trebicka, Peer Bork, Aleksander Krag & Manimozhiyan Arumugam

Nature Reviews Gastroenterology & Hepatology volume 18, pages167–180(2021)Cite this article

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Abstract

The human gut microbiome has emerged as a major player in human health and disease. The liver, as the first organ to encounter microbial products that cross the gut epithelial barrier, is affected by the gut microbiome in many ways. Thus, the gut microbiome might play a major part in the development of liver diseases. The common end stage of liver disease is decompensated cirrhosis and the further development towards acute-on-chronic liver failure (ACLF). These conditions have high short-term mortality. There is evidence that translocation of components of the gut microbiota, facilitated by different pathogenic mechanisms such as increased gut epithelial permeability and portal hypertension, is an important driver of decompensation by induction of systemic inflammation, and thereby also ACLF. Elucidating the role of the gut microbiome in the aetiology of decompensated cirrhosis and ACLF deserves further investigation and improvement; and might be the basis for development of diagnostic and therapeutic strategies. In this Review, we focus on the possible pathogenic, diagnostic and therapeutic role of the gut microbiome in decompensation of cirrhosis and progression to ACLF.
Key points

    The gut microbiome is altered during development of liver cirrhosis, and these changes are associated with decompensation and development of acute-on-chronic liver failure (ACLF).

    Progression of liver cirrhosis towards decompensation and ACLF is mainly driven by the extent of systemic inflammation and associated with high short-term mortality.

    The gut microbiota can contribute to systemic inflammation and, thereby, to progression of cirrhosis towards decompensation and ACLF, directly via translocation or indirectly via their metabolites.

    Gut microbiota members or pathobionts might be helpful biomarkers to predict the presence and development of decompensation and ACLF, but the signatures are not consistent and more research is needed.

    Gut microbiome targeted therapies are promising strategies to improve the outcome of decompensated cirrhosis and ACLF, but better stratification for the existing drugs and novel, more effective strategies are needed.

StephenW

利用肠道微生物组治疗失代偿性肝硬化和急性慢性肝功能衰竭

    Jonel Trebicka，Peer Bork，Aleksander Krag和Manimozhiyan Arumugam

自然评论，胃肠病和肝病，第18卷，第167–180页（2021），引用本文

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抽象的

人体肠道微生物组已成为人类健康和疾病的主要参与者。肝脏作为第一个遇到穿过肠道上皮屏障的微生物产物的器官，在许多方面受到肠道微生物组的影响。因此，肠道微生物组可能在肝脏疾病的发展中起主要作用。肝病的常见终末期是代偿性肝硬化，并逐渐发展为慢性慢性肝功能衰竭（ACLF）。这些情况具有很高的短期死亡率。有证据表明，通过不同的致病机制（例如增加的肠道上皮通透性和门脉高压）促进的肠道菌群组成部分的易位是诱导全身性炎症从而引起失代偿的重要驱动力，因此也是ACLF的重要驱动力。阐明肠道微生物组在失代偿性肝硬化和ACLF病因中的作用值得进一步研究和改进；并可能是制定诊断和治疗策略的基础。在这篇综述中，我们重点研究肠道微生物组在肝硬化失代偿和发展为ACLF中可能的致病，诊断和治疗作用。
关键点

    肠道微生物组在肝硬化发展过程中发生了变化，这些变化与失代偿和急性慢性肝功能衰竭（ACLF）的发展有关。

    肝硬化向代偿失调和ACLF的进展主要由全身炎症的程度驱动，并伴有较高的短期死亡率。

    肠道菌群可导致全身性炎症，从而直接或通过其代谢产物，促进肝硬化向代偿失调和ACLF的发展。

    肠道菌群成员或病原体可能是预测失代偿和ACLF的存在和发展的有用的生物标志物，但特征并不一致，需要更多的研究。

    肠道微生物组靶向治疗是改善失代偿性肝硬化和ACLF结局的有前途的策略，但是对现有药物进行更好的分层和新的，更有效的策略是必需的。