Gastrodia elata Blume water extract modulates neurotransmitters and alters the gut microbiota in a mild social defeat stress‐induced depression mouse model

Gastrodia elata Blume has multiple bioactive functions, such as antioxidant and antidepressant activities, immune modulation, neuroplasticity, and neuroprotection. We previously found that the water extract of G. elata exerts antidepressant‐like effects in unpredictable chronic mild stress models and animals exposed to the forced swimming test. We aimed to investigate the mechanisms by which the water extract of G. elata protects against subchronic‐ and mild‐social defeat‐stress‐induced dysbiosis. After a 10‐day subchronic and mild‐social‐defeat‐stress program, oral treatment with the water extract of G. elata (500 mg/kg bw) resulted in reversal of depression‐like behavior. In addition, monoamine analyses showed that the water extract of G. elata normalized the 5‐hydroxyindoleacetic acid:5‐HT ratio in the prefrontal cortex and colon and reduced the defeat‐stress‐induced kynurenine:tryptophan ratio in the colon. After the 10‐day subchronic and mild social‐defeat‐stress program, the water extract of G. elata altered the intestinal microbiome by increasing Actinobacteria levels, modulating intestinal inflammation, and shifting the relative abundances of multiple bacterial groups in the gut. Our results suggest that the water extract of G. elata exhibits a potent antidepressant‐like effect via the regulation of monoaminergic neurotransmission and alteration of gut microbiota composition and function, and that it may be an effective prevention for depression.