Schnabl Bernd, Damman Christopher J, Carr Rotonya M
Department of Medicine, Division of Gastroenterology, UCSD, San Diego, California, USA.
Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA.
J Clin Invest. 2025 Apr 1;135(7):e186423. doi: 10.1172/JCI186423.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis. We explore the complexity and importance of the intestinal barrier function and how disruptions of the intestinal barrier and dysbiosis work in concert to promote the onset and progression of MASLD. The Review focuses on specific bacterial, viral, and fungal communities that impact the trajectory of MASLD and how specific metabolites (including ethanol, bile acids, short chain fatty acids, and other metabolites) contribute to disease pathogenesis. Finally, we underscore how knowledge of the interaction between gut microbes and the intestinal barrier may be leveraged for MASLD microbial-based therapeutics. Here, we include a discussion of the therapeutic potential of prebiotics, probiotics, postbiotics, and microbial-derived metabolites.
代谢功能障碍相关脂肪性肝病（MASLD）是全球肝病的主要病因，我们对其发病机制的认识仍在不断发展。MASLD 从脂肪变性发展为脂肪性肝炎、纤维化和肝硬化，本综述探讨了肠道微生物群及其代谢产物如何促成 MASLD 的发病机制。我们探讨了肠道屏障功能的复杂性和重要性，以及肠道屏障破坏和生态失调如何协同作用促进 MASLD 的发生和发展。本综述重点关注影响 MASLD 病程的特定细菌、病毒和真菌群落，以及特定代谢产物（包括乙醇、胆汁酸、短链脂肪酸和其他代谢产物）如何促成疾病发病机制。最后，我们强调如何利用肠道微生物与肠道屏障之间相互作用的知识来开发基于微生物的 MASLD 治疗方法。在此，我们讨论了益生元、益生菌、后生元及微生物衍生代谢产物的治疗潜力。
