Xiong Feixiang, Zhang Xuejie, Jiang Yuyong, Meng Peipei, Zhou Yang, Ji Xiaomin, Chen Jialiang, Wu Tong, Hou Yixin
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing 100015, China.
Metabolites. 2024 Dec 4;14(12):681. doi: 10.3390/metabo14120681.
The prevalence and adverse outcomes of metabolic dysfunction associated with steatotic liver disease (MAFLD) are increasing. The changes in the gut microbiota and metabolites associated with metabolic dysfunction-associated steatohepatitis (MASH) are regarded as an essential part of the progression of MAFLD. This study aimed to identify the gut microbiota and metabolites involved in the development of MAFLD in patients.
This study enrolled 90 patients (healthy controls, HC: = 30; MASH: = 30; MASH-related cirrhosis, MC: = 30), and their fecal samples were collected for 16S rRNA sequencing and non-targeted LC-MS/MS metabolomics analysis. Data preprocessing and statistical analyses were performed using QIIME2 software, Pynast, QIIME2 package, Progenesis QI, and R program.
The abundance of Prevotellaceae at the family level and Prevotella at the genus level was lower in the MASH and NC samples than in the HC samples. Both Prevotellaceae and Prevotella showed the strongest correlation with MASH progression via random forest analysis. Untargeted metabolomics was used to quantitatively screen for discrepant metabolites in the stool samples from the three groups. Linolenic acid (LA)-related metabolite levels were significantly lower in MASH and NC samples. Associations between Prevotella- or LA-related metabolites and liver function were discovered. A high abundance of Prevotella was associated with LA-related metabolites and MASH.
This study identified that gut microbiota and metabolites are associated with MASH-related metabolic dysfunction. LA and Prevotella are depleted during MASH progression, and additional supplementation with Prevotella may be a potential strategy for the future treatment of MAFLD.
与脂肪性肝病相关的代谢功能障碍（MAFLD）的患病率和不良后果正在增加。肠道微生物群和与代谢功能障碍相关的脂肪性肝炎（MASH）的代谢物变化被认为是MAFLD进展的重要组成部分。本研究旨在确定参与MAFLD患者发病过程的肠道微生物群和代谢物。
本研究纳入90例患者（健康对照，HC：=30；MASH：=30；MASH相关肝硬化，MC：=30），收集他们的粪便样本进行16S rRNA测序和非靶向LC-MS/MS代谢组学分析。使用QIIME2软件、Pynast、QIIME2软件包、Progenesis QI和R程序进行数据预处理和统计分析。
在MASH和NC样本中，科水平的普雷沃氏菌科和属水平的普雷沃氏菌的丰度低于HC样本。通过随机森林分析，普雷沃氏菌科和普雷沃氏菌与MASH进展的相关性最强。使用非靶向代谢组学对三组粪便样本中的差异代谢物进行定量筛选。MASH和NC样本中与亚麻酸（LA）相关的代谢物水平显著降低。发现了普雷沃氏菌或与LA相关的代谢物与肝功能之间的关联。高丰度的普雷沃氏菌与LA相关代谢物和MASH有关。
本研究确定肠道微生物群和代谢物与MASH相关的代谢功能障碍有关。在MASH进展过程中，LA和普雷沃氏菌减少，额外补充普雷沃氏菌可能是未来治疗MAFLD的潜在策略。
