北京大学姜长涛研究小组近日取得一项新成果。经过不懈努力，他们开发出微生物源氨基酸偶联胆汁酸——色氨酸-胆酸通过孤儿受体MRGPRE改善葡萄糖稳态。2025年5月29日出版的《细胞》杂志发表了这项成果。
该课题组人员发现色氨酸共轭胆酸（Trp-CA）是2型糖尿病（T2D）患者中最显著降低的MABA，其丰度与临床血糖指标呈负相关。研究组进一步证明了Trp-CA可以改善糖尿病小鼠的葡萄糖耐量。在机制上，该团队发现Trp-CA是孤儿G蛋白偶联受体（GPCR）Mas相关G蛋白偶联受体家族成员E（MRGPRE）的配体，并确定了两者之间的结合方式。MRGPRE-Gs-cyclic AMP（cAMP）和MRGPRE-β-arrestin-1-醛缩酶A （ALDOA）信号通路都有助于Trp-CA的代谢益处。此外，研究小组发现双歧杆菌的胆汁盐水解酶/转移酶负责Trp-CA的产生。总之，他们的发现为进一步研究MABA铺平了道路，并为治疗T2D提供了额外的治疗靶点。
据介绍，近年来，微生物源氨基酸偶联胆汁酸（MABAs）已被发现在人体样本中普遍存在。然而，它们的生理意义尚不清楚。
附：英文原文
Title: A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE
Author: Jun Lin, Qixing Nie, Jie Cheng, Ya-Ni Zhong, Tianyao Zhang, Xiuying Zhang, Xiaoyan Ge, Yong Ding, Canyang Niu, Yuhua Gao, Kai Wang, Mingxin Gao, Xuemei Wang, Weixuan Chen, Chuyu Yun, Chuan Ye, Jinkun Xu, Weike Shaoyong, Lijun Zhang, Pan Shang, Xi Luo, Zhiwei Zhang, Xin Zheng, Xueying Sha, Jinxin Zhang, Shaoping Nie, Xuguang Zhang, Fazheng Ren, Huiying Liu, Erdan Dong, Xiao Yu, Linong Ji, Yanli Pang, Jin-Peng Sun, Changtao Jiang
Issue&Volume: 2025-05-29
Abstract: Recently, microbial amino-acid-conjugated bile acids (MABAs) have been found to be prevalent in human samples. However, their physiological significance is still unclear. Here, we identify tryptophan-conjugated cholic acid (Trp-CA) as the most significantly decreased MABA in patients with type 2 diabetes (T2D), and its abundance is negatively correlated with clinical glycemic markers. We further demonstrate that Trp-CA improves glucose tolerance in diabetic mice. Mechanistically, we find that Trp-CA is a ligand of the orphan G protein-coupled receptor (GPCR) Mas-related G protein-coupled receptor family member E (MRGPRE) and determine the binding mode between the two. Both MRGPRE-Gs-cyclic AMP (cAMP) and MRGPRE-β-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits of Trp-CA. Additionally, we find that the bacterial bile salt hydrolase/transferase of Bifidobacterium is responsible for the production of Trp-CA. Together, our findings pave the way for further research on MABAs and offer additional therapeutic targets for the treatment of T2D.
DOI: 10.1016/j.cell.2025.05.010
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00560-4