人体肠道真菌对陈诺二氧化醇酸的生物转化以及对FXR的激活作用
Xuemei Wei1, Changliang Yao2, Xin He2
1National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Pharmaceutical Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
Phytochemistry
|May 26, 2024
概括
人体肠道真菌将初级胆汁酸陈氧胆酸 (CDCA) 转化为新型化合物. 其中一些新化合物抑制了Farnesoid X受体 (FXR),影响了宿主代谢.
科学领域:
- 微生物学 微生物学
- 代谢学 代谢学 代谢学
- 生物化学 生化学
背景情况:
- 胆汁酸,如陈二氧化醇酸 (CDCA),对于宿主代谢至关重要.
- CDCA自然激活了Farnesoid X受体 (FXR),这是代谢过程的关键调节者.
研究的目的:
- 为了研究人类肠道真菌对CDCA的微生物转化.
- 识别新的CDCA代谢物并评估它们对FXR活性的影响.
主要方法:
- 用七种人类肠道真菌物种化CDCA.
- 使用高分辨率电喷射电离质谱仪 (HRESI-MS) 和核磁共振 (NMR) 数据阐明产生的化合物的结构.
- 在体外测试以评估已识别的化合物的FXR调制.
主要成果:
- 化和脱是观察到的主要代谢途径.
- 使用Rhizopus微胞子进行化,产生了8种新化合物和5种已知的类似物.
- 化合物8,12和13对FXR活性表现出抑制作用,与CDCA的激活形成鲜明对比.
结论:
- 人类肠道真菌通过基化和脱而显著转化CDCA.
- 由真菌产生的新型CDCA衍生物可以调节FXR活性,作为抑制剂.
- 这些发现强调了真菌代谢在塑造胆酸信号传递中的作用,并为代谢疾病干预提供了潜在的目标.
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