Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a tradi-tional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mech-anism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut mi-crobial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance beha-vior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutter-ella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration in-duced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid meta-bolism to alleviate stress-induced depression.