On May 29, the research teams led by Professors Sun Jinpeng and Yu Xiao from Shandong University, in collaboration with the teams led by Professors Jiang Changtao, Pang Yanli, and Ji Linong from Peking University, published a research paper titled “A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE” in the journal Cell. The study revealed the physiological and pathophysiological functions of tryptophan-cholic acid (Trp-CA), a novel microbiota-derived amino-acid-conjugated bile acid, identified MRGPRE (Mas-related G protein-coupled receptor family member E) as the membrane receptor of Trp-CA, and elaborated in depth on a novel mechanism. Specifically, Trp-CA activates MRGPRE, which then promotes the secretion of GLP-1 (Glucagon-like peptide-1) through the Gs-cAMP signaling pathway and the phosphorylation of β-arrestin-1-ALDOA. This work provides a new paradigm for exploring the functions and molecular mechanisms of novel microbiota-derived bile acids, and offers new targets and strategies for the development of drugs for metabolic diseases.