Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Oslo, Norway.
Hepatology. 2024 Oct 1;80(4):965-987. doi: 10.1097/HEP.0000000000000506. Epub 2023 Jun 27.
The microbiome plays a crucial role in integrating environmental influences into host physiology, potentially linking it to autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. All autoimmune liver diseases are associated with reduced diversity of the gut microbiome and altered abundance of certain bacteria. However, the relationship between the microbiome and liver diseases is bidirectional and varies over the course of the disease. This makes it challenging to dissect whether such changes in the microbiome are initiating or driving factors in autoimmune liver diseases, secondary consequences of disease and/or pharmacological intervention, or alterations that modify the clinical course that patients experience. Potential mechanisms include the presence of pathobionts, disease-modifying microbial metabolites, and more nonspecific reduced gut barrier function, and it is highly likely that the effect of these change during the progression of the disease. Recurrent disease after liver transplantation is a major clinical challenge and a common denominator in these conditions, which could also represent a window to disease mechanisms of the gut-liver axis. Herein, we propose future research priorities, which should involve clinical trials, extensive molecular phenotyping at high resolution, and experimental studies in model systems. Overall, autoimmune liver diseases are characterized by an altered microbiome, and interventions targeting these changes hold promise for improving clinical care based on the emerging field of microbiota medicine.
微生物组在将环境影响整合到宿主生理学中起着至关重要的作用，它可能与自身免疫性肝病有关，如自身免疫性肝炎、原发性胆汁性胆管炎和原发性硬化性胆管炎。所有自身免疫性肝病都与肠道微生物组多样性降低和某些细菌丰度改变有关。然而，微生物组与肝脏疾病之间的关系是双向的，并在疾病过程中发生变化。这使得解析微生物组的这种变化是自身免疫性肝病的起始或驱动因素、疾病和/或药物干预的继发后果，还是改变患者所经历的临床病程的因素变得具有挑战性。潜在的机制包括病原体的存在、改变疾病的微生物代谢产物，以及更非特异性的肠道屏障功能降低，并且在疾病进展过程中很可能会发生这些变化的影响。肝移植后疾病复发是这些疾病的一个主要临床挑战和共同特征，这也可能代表着对肠道-肝脏轴疾病机制的一个窗口。在此，我们提出了未来的研究重点，这些重点应该包括临床试验、高分辨率的广泛分子表型分析以及模型系统中的实验研究。总的来说，自身免疫性肝病的特点是微生物组发生改变，针对这些变化的干预措施有望基于新兴的微生物组医学领域改善临床护理。
