JINAN, China, June 23, 2025 /PRNewswire/ — On May 29, 2025, Professor Sun Jinpeng’s team and Professor Yu Xiao’s team at Shandong University, collaborating with Professor Jiang Changtao from Peking University, Professor Pang Yanli, and Professor Ji Linong, published a research paper entitled “A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE” in Cell.
The study revealed the physiological and pathophysiological functions of a novel microbial-derived amino acid-conjugated bile acid, tryptophan-cholic acid (Trp-CA). It identified the membrane receptor for Trp-CA as MRGPRE. It elucidated the novel mechanism by which Trp-CA activates MRGPRE, promoting GLP-1 secretion through dual pathways: Gs-cAMP signaling and β-arrestin-1-mediated ALDOA phosphorylation, thereby improving glucose metabolism. This work provides a new paradigm for understanding the functions and molecular mechanisms of novel microbial bile acids. It offers new targets and strategies for the development of therapies against metabolic diseases.
This research is the first to reveal that the microbial-derived bile acid Trp-CA improves glucose homeostasis by activating MRGPRE. It provides a new potential drug target and therapeutic strategy for Type 2 Diabetes (T2D) treatment. Furthermore, the identification of the microbial origin of Trp-CA offers a new microbial therapeutic strategy for diabetes intervention.
