Recently, Professor Dai Yue's team from the School of Traditional Chinese Medicine published their latest research findings in the top-tier journal Advanced Science, titled “7-Ketodeoxycholic Acid Promotes Colonic Mucosal Healing by Inducing Calcium Release from Endoplasmic Reticulum via the TGR5-IP3R Pathway.” This study explores the pivotal role of bile acid metabolites in intestinal mucosal repair, offering novel insights for treating ulcerative colitis (UC).
Impaired mucosal healing is a core pathological feature in UC and other diseases, severely impacting patients' quality of life and long-term prognosis. While mucosal healing has become a key therapeutic target for UC, the endogenous metabolites that effectively promote intestinal epithelial repair remain unclear.
Through systematic screening, the research team discovered significantly reduced levels of multiple bile acids in the serum of UC patients and colitis model mice, with the most pronounced downregulation observed for 7-ketodeoxycholic acid (7-KDCA). Its concentration was negatively correlated with disease severity. Among various bile acids, 7-KDCA exhibited the strongest mucosal repair-promoting effect. Exogenous supplementation of 7-KDCA significantly accelerated colonic mucosal healing in mice with DSS-induced and biopsy-induced intestinal injury models. Mechanistic studies revealed that 7-KDCA does not act through conventional anti-inflammatory immune pathways but directly targets intestinal epithelial cells. By activating the TGR5-IP3R signaling axis, it induces calcium release from the endoplasmic reticulum, thereby enhancing epithelial cell migration and driving wound closure. This discovery provides a novel therapeutic target and theoretical basis for mucosal repair. Zhang Jing, a doctoral candidate at the School of Chinese Medicine, is the first author of this paper. Professors Dai Yue and Xia Yufeng are the co-corresponding authors.
This research was supported by the National Natural Science Foundation of China (82174049, 82174372) and the “Double First-Class” Discipline Innovation Team Construction Project of China Pharmaceutical University (CPU2022QZ31).
Full text link: https://doi.org/10.1002/advs.202507953
