肠共生体通过二次胆酸生物合成途径缓解MASH
Qixing Nie1, Xi Luo2, Kai Wang3
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; State Key Laboratory of Food Science and Resources, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China.
研究人员发现了一种新的肠道微生物产生的胆酸,3-sucCA,通过促进有益的肠道细菌,可能有助于控制代谢功能障碍相关的脂肪肝炎 (MASH).
科学领域:
- 微生物学
- 胃肠病学
- 代谢疾病
背景情况:
- 肠道微生物群在代谢功能障碍相关的脂肪肝炎 (MASH) 中的作用是显著的,但在机制上尚不清楚.
- 鉴定涉及MASH病变的特定微生物代谢物对于治疗发展至关重要.
研究的目的:
- 为了确定MASH中涉及的微生物衍生胆酸.
- 阐明这些代谢物影响肝脏健康和疾病进展的机制.
主要方法:
- 开发基于点击化学的丰富策略以识别微生物代谢物.
- 对人类细菌分离物进行胆汁酸生产的查.
- 基于活动的蛋白质净化,以确定负责代谢物生物合成的酶.
- 在体外和体内验证代谢物的产生和功能.
主要成果:
- 一种新型的微生物胆汁酸3-sucCA的鉴定.
- 在与代谢功能失调相关的脂肪肝病 (MAFLD) 患者中,3- sucCA水平与肝损伤之间的负相关性.
- 鉴于此,巴克特罗伊德 (Bacteroides uniformis) 已被确定为3-sucCA的主要生产者.
- 在B. uniform中有一种β- 乳糖酶被证实是对3- 糖生物合成的负责者.
- 通过增强Akkermansia muciniphila的生长来缓解MASH,3- sucCA被证明是一个光度受限的代谢物.
结论:
- 3-sucCA是一种新的肠道微生物代谢物,对MASH具有潜在的治疗意义.
- 肠道微生物群-肝脏轴通过调节特定的微生物代谢物,如3-sucCA,为MASH管理提供了目标.
- 针对B. uniformis或3-sucCA的生产可能是改善MASH结果的策略.
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