Gut microbiota has emerged as a crucial target of gut-brain axis to influence depression. Zhi-Zi-Chi decoctions (ZZCD), as a classic oral formula in clinic, is widely applied in depression treatment nowadays. However, the underlying mechanism in the
antidepressant activity of ZZCD remains unknown. A classic depression model of chronic mild unpredictable stress (CUMS) was established in rats based on the results of behavioral tests and hippocampal histomorphology.
16S rRNA sequencing analysis indicated that ZZCD could increase
short-chain fatty acid-producing and anti-inflammatory bacteria and reduce inflammatory and
tryptophan-metabolizing bacteria. Furthermore, ZZCD reversed the alterations of
BDNF, TNF-α, pro-inflammatory
cytokines and
neurotransmitters in the gut, blood and brain along the brain-gut axis and restored the decrease of
butyrate in cecal content caused by CUMS. Then,
butyrate was utilized to validate its ameliorative effect on pathological characteristics of depressive rats. Taken together, these results show that ZZCD exhibits
antidepressant effect through modulating gut microbiota to facilitate the production of
butyrate, which further regulate anti-
inflammation,
neurotransmitters, endocrine and
BDNF along the gut-brain axis. Hence, this study fills the gap of the antidepressive mechanism of ZZCD in the light of the brain-gut axis and established a multi-targets and multi-levels platform eventually for further research into the mechanism of other TCM efficacy.