肠道共体细菌中的三胺代谢和功能扩大人类的三胺信号响应
Hyun Bong Park1,2,3, Deguang Song4, Mytien Nguyen4
1Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
ACS chemical biology
|June 27, 2025
概括
研究人员发现了来自肠道细菌的新分子,可以激活人类的黑色素受体和其他点. 一个分子,1,也抑制了炎症酶,并影响小鼠的CD8 T细胞.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
背景情况:
- 肠道微生物产生各种各样的小分子,影响人类生理学.
- 已知肠道衍生功能分子的库存仍然有限.
- G蛋白结合受体 (GPCR) 是微生物代谢物的关键标.
研究的目的:
- 选人类便衍生的细菌超级生物,以检测黑色素受体MTNR1A和MTNR1B的激动剂.
- 为了识别和描述来自*Clostridium sporogenes*具有GPCR激活活性的新型小分子.
主要方法:
- 查细菌超级生物的GPCR活性.
- 生物活性辅助的分离和代谢物的化学表征.
- 合成已识别的化合物用于结构确认.
- 进行GPCR查和酶抑制试验.
- 在小鼠模型中进行单细胞RNA测序分析.
主要成果:
- 从*C. sporogenes*中确定了三种胺衍生代谢物 (1-3),其中包括两种新型化合物.
- 化合物2激活了黑色素受体和P2RY11.
- 化合物1激活了GPR55并抑制了可溶性环氧化酶 (sEH),其IC50为420nm.
- 口服化合物1降低了小鼠肠内皮质淋巴细胞中的GPR55+和K+CD8 T细胞.
结论:
- 这项研究扩大了已知的肠道微生物代谢物的化学多样性.
- 已识别的化合物调节关键宿主受体和酶,影响免疫细胞群.
- 肠道细菌中的三胺代谢是生物活性信号分子的重要来源.
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