The FXR mediated anti-depression effect of CDCA underpinned its therapeutic potentiation for MDD

•The plasma CDCA were significantly lower in Chinese MDD patients than in healthy subjects.•After antidepressant treatment, the low plasma CDCA in MDD patients were rescued in remitters but not in nonremitters.•Plasma CDCA was reduced in CSDS mice, and CDCA treatment restored the level of FXR, inhibited NLRP3 inflammasome, increased the GluA1 levels in the PFC, and inhibited the plasma inflammatory cytokines.•CDCA showed antidepressant efficacy in CSDS mice, which were abolished by FXR blocker.