Martin-Grau Maria, Monleón Daniel
Department of Pathology, University of Valencia, 46010 Valencia, Spain.
University Clinical Hospital of Valencia Research Foundation (INCLIVA), 46010 Valencia, Spain.
Curr Issues Mol Biol. 2024 Jun 25;46(7):6377-6389. doi: 10.3390/cimb46070381.
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing health concern due to its increasing prevalence worldwide. Metabolic homeostasis encompasses the stable internal conditions vital for efficient metabolism. This equilibrium extends to the intestinal microbiota, whose metabolic activities profoundly influence overall metabolic balance and organ health. The metabolites derived from the gut microbiota metabolism can be defined as microbiota-related co-metabolites. They serve as mediators between the gut microbiota and the host, influencing various physiological processes. The recent redefinition of the term MASLD has highlighted the metabolic dysfunction that characterize the disease. Metabolic dysfunction encompasses a spectrum of abnormalities, including impaired glucose regulation, dyslipidemia, mitochondrial dysfunction, inflammation, and accumulation of toxic byproducts. In addition, MASLD progression has been linked to dysregulation in the gut microbiota and associated co-metabolites. Short-chain fatty acids (SCFAs), hippurate, indole derivatives, branched-chain amino acids (BCAAs), and bile acids (BAs) are among the key co-metabolites implicated in MASLD progression. In this review, we will unravel the relationship between the microbiota-related metabolites which have been associated with MASLD and that could play an important role for developing effective therapeutic interventions for MASLD and related metabolic disorders.
代谢功能障碍相关脂肪性肝病（MASLD）因其在全球范围内的患病率不断上升，已成为一个日益严重的健康问题。代谢稳态包括对高效代谢至关重要的稳定内部条件。这种平衡延伸到肠道微生物群，其代谢活动深刻影响整体代谢平衡和器官健康。源自肠道微生物群代谢的代谢产物可被定义为微生物群相关的共代谢产物。它们充当肠道微生物群与宿主之间的介质，影响各种生理过程。最近对MASLD这一术语的重新定义突出了该疾病所特有的代谢功能障碍。代谢功能障碍包括一系列异常，包括葡萄糖调节受损、血脂异常、线粒体功能障碍、炎症以及有毒副产物的积累。此外，MASLD的进展与肠道微生物群和相关共代谢产物的失调有关。短链脂肪酸（SCFAs）、马尿酸盐、吲哚衍生物、支链氨基酸（BCAAs）和胆汁酸（BAs）是与MASLD进展相关的关键共代谢产物。在本综述中，我们将阐明与MASLD相关且可能在开发针对MASLD及相关代谢紊乱的有效治疗干预措施中发挥重要作用的微生物群相关代谢产物之间的关系。
