在非酒精性脂肪肝疾病的发展过程中,肝细胞TM4SF5表达和肠道微生物组失调之间存在关联
Yangie Dwi Pinanga1, Kyung-Hee Pyo1, Eun-Ae Shin1
1Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Life sciences
|October 25, 2024
概括
肝细胞TM4SF5过度表达通过改变肠道微生物群,增加有害细菌和减少有益细菌来促进非酒精性脂肪性肝病 (NAFLD). 这种失生症与短链脂肪酸的产生和肝炎有关.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物学 微生物学
- 代谢疾病 代谢疾病
背景情况:
- 肠道微生物组失调症与非酒精性脂肪性肝病 (NAFLD) 的病原发生有关.
- 肝转膜L6家族成员5 (TM4SF5) 过度表达是已知的NAFLD促进者.
- 肠道微生物群和TM4SF5驱动的NAFLD之间的具体联系仍然不太清楚.
研究的目的:
- 研究TM4SF5表达,饮食因素和肠道微生物组合在NAFLD发展中的关联.
- 探索肠道微生物组与TM4SF5介导的NAFLD相关的功能途径.
主要方法:
- 在转基因 (TG) 过度表达TM4SF5的小鼠和缺少TM4SF5.5的淘汰 (KO) 小鼠上进行了便肠道微生物组分析.
- 小鼠接受了正常的饮食 (NCD),高脂肪饮食 (HFD) 2 周,或甲胺-胆缺乏饮食 (MCD) 4 周.
- 相关性分析被用来将微生物组资料与NAFLD特征和代谢途径联系起来.
主要成果:
- 肝细胞中的TM4SF5过度表达导致了肠道微生物组合的改变,包括增加了Firmicutes与Bacteroidetes的比率,并减少了像Akkermansia muciniphila和Lactobacillus reuteri这样的有益细菌.
- 与NASH相关的微生物组在超表达TM4SF5的小鼠中比HFD更为普遍.
- 用MCD养的TM4SF5过度表达的小鼠表现出更高的F/B比率和微生物种群的变化,与短链脂肪酸 (SCFA) 生产和NAFLD进展相关.
结论:
- 肝细胞TM4SF5表达显著影响肠道微生物组合和功能.
- TM4SF5介导的肠道失调有助于NAFLD通过改变SCFA生产和肝炎的发展.
- 针对TM4SF5或肠道微生物群可能为NAFLD提供治疗策略.
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