在MASLD小鼠模型中,肠道微生物群和胆汁酸的变化与肝脏PLD1的淘汰赛
Yushang Zhao1, Huan Wang2, Wanling Lin1
1Department of Clinical Laboratory, Peking University People's Hospital, Beijing 100044, China.
Acta biochimica et biophysica Sinica
|October 24, 2025
概括
在小鼠中,肝细胞脂酶D1 (PLD1) 淘汰赛通过改变肠道微生物群和胆酸概况,改善了与代谢功能障碍相关的脂肪性肝病 (MASLD). 这表明PLD1缺陷影响了MASLD通过肠肝轴恒温的进展.
科学领域:
- 肝病学和胃肠病学 肝病学和胃肠学
- 微生物组研究 微生物组研究
- 代谢疾病机制 代谢疾病机制
背景情况:
- 肝细胞脂酶D1 (PLD1) 淘汰赛在小鼠中缓解了与代谢功能障碍相关的脂肪性肝病 (MASLD).
- 在MASLD中PLD1的作用背后的精确分子机制在很大程度上仍未被阐明.
- 了解PLD1对肠道微生物群和胆酸代谢的影响对于MASLD的发病过程至关重要.
研究的目的:
- 在小鼠模型中研究肝细胞PLD1淘汰对MASLD的影响的潜在机制.
- 分析PLD1缺乏对肠道微生物群组成和胆酸概况的影响.
- 探索特定肠道细菌,胆酸和MASLD中的肝脏状况之间的相关性.
主要方法:
- 建立了四个小鼠组:控制,高脂肪/高胆固醇饮食 (HFHC),控制饮食中的PLD1淘汰赛 (KO) 和HFHC饮食中的PLD1KO.
- 使用元基因组学和代谢学分析肠道内容.
- 通过质谱成像评估的肝胆酸.
主要成果:
- 在MASLD模型小鼠中,Bacillota增加和Bacteroidota减少;在PLD1 KO小鼠中,Pseudomonadota和Candidatus Bathyarchaeota减少.
- 在MASLD小鼠中,特定的细菌物种如*Faecalibaculum rodentium*增加,而PLD1 KO减少了*Desulfovibrionaceae细菌* LT0009和*Lachnospiraceae细菌* 10-1.
- PLD1淘汰改变了肠道胆汁酸 (氧胆汁酸,甘油胆汁酸) 和降低了肝脏TCA和TDCA水平,将肠道微生物群的变化与胆汁酸变化相关联.
结论:
- 肝细胞PLD1淘汰显著改变了MASLD小鼠的肠道微生物群组成和胆酸概况.
- 似乎PLD1缺陷通过影响肠道微生物群和胆汁酸代谢之间的复杂平衡来调节MASLD的进展.
- 针对PLD1可能通过重新平衡肠肝轴信号来为MASLD提供一种新的治疗策略.
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