口服可以通过调节微生物代谢来预防乙氨基引起的急性肝损伤
Dongping Li1, Yu Chen2, Meijuan Wan1
1Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Cell host & microbe
|December 6, 2023
概括
口服 (Mg) 通过改变肠道细菌来对抗乙氨基引起的急性肝衰竭 (ALF). 丰富了英多尔-3-碳素酸 (I3C),抑制了有毒的CYP2E1酶,保护肝脏.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物组研究 微生物组研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 乙氨基 (APAP) 过量服用是急性肝衰竭 (ALF) 的主要原因之一.
- CYP2E1将APAP代谢成有毒的活性物种,导致氧化应激和肝损伤.
- 人们越来越认识到肠道微生物组在APAP诱导的ALF中的作用.
研究的目的:
- 研究口服 (Mg) 对APAP诱导的ALF的保护作用.
- 阐明Mg调节肠道微生物群以防止肝损伤的机制.
- 为了确定特定的微生物代谢物和酶参与Mg的肝保护作用.
主要方法:
- 向小鼠和人类口服Mg,然后诱导与APAP相关的ALF.
- 分析了肠道微生物组成和新陈代谢的变化,使用元基因组学和代谢学.
- 利用淘汰和工程细菌菌株来确认特定微生物通路的作用.
- 评估了肝脏组织中的CYP2E1活性和氧化应激标志物.
主要成果:
- 口服Mg在小鼠中显著缓解了APAP诱导的ALF.
- 补充Mg改变了肠道微生物群,增加了英多尔-3-碳酸 (I3C) 水平.
- 一个关键的Bifidobacterium酶,形式C-乙转移酶 (pflB),被确定为I3C生成的关键.
- I3C直接抑制了CYP2E1,减少了有毒代谢物形成和肝细胞损伤.
结论:
- 通过肠道微生物群调节对APAP诱导的ALF产生肝保护作用.
- 通过Bifidobacterium pflB丰富I3C是Mg有益作用的关键机制.
- 针对肠道微生物群,特别是I3C生产,为ALF提供了一个新的治疗策略.
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