Teadenol A, a Key Cleavage Product of EGCG in Dark Tea, Alleviates Depressive‐Like Behavior by Modulating the Microbiota–Gut–Brain Axis in CUMS‐Induced Rats

Depression is a chronic mental disorder that impacts human health. The potential antidepressant effects of teadenol A—the primary cleavage product of the EGCG B‐ring formed during dark tea processing—remain unclear. In this study, a CUMS‐induced rat model of depression was used to preliminarily investigate the potential antidepressant effects of teadenol A through the microbiota–gut–brain axis. The results indicated that teadenol A alleviated depressive behaviors, reduced serum inflammatory factors, improved hippocampal morphology, and upregulated BDNF expression in CUMS‐induced depressed rats. Additionally, teadenol A reshaped the gut microbiota profile, leading to an increased relative abundance of beneficial bacteria, such as Monoglobus , Akkermansia , Quinella , and the Lachnospiraceae NK4A136 group . Untargeted metabolomics analysis revealed that teadenol A mitigated metabolic dysregulation in feces, colon, serum, and cerebral cortex of depressed rats, while partially restoring metabolite profiles to a homeostatic state. Targeted metabolomics results further showed that teadenol A promoted BAs and SCFAs metabolism in feces, while significantly increasing Trp contents in serum. Collectively, these findings suggest that teadenol A has potential antidepressant effects in alleviating CUMS‐induced depression‐like behaviors by regulating gut microbiota and metabolomic imbalances through the microbiota–gut–brain axis.