Semen Sojae Praeparatum alters depression-like behaviors in chronic unpredictable mild stress rats via intestinal microbiota

A large number of Chinese medical books present that Semen Sojae Praeparatum, a fermented food, possesses antidepressant effect, but the mechanism of this antidepressant effect remains largely unknown. This study aimed to explore the effect of Semen Sojae Praeparatum on rats with chronic unpredictable mild stress (CUMS)-induced depression. The results showed that Semen Sojae Praeparatum improved depression-like behaviors (negative preference of sugar water and increased swimming immobility time and time spent in the dark zone) and effectively reduced cell morphological changes in the dentate gyrus of the hippocampus in CUMS rats. In addition, Semen Sojae Praeparatum significantly promoted the contents of norepinephrine (NE), 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and gamma-aminobutyric acid (GABA) in the hippocampus and the content of BDNF in the serum (p < 0.05). 16S rRNA sequencing analysis results showed that Semen Sojae Praeparatum increased the abundance of genus Ruminococcaceae_UCG-008 and decreased those of genera Lactobacillus and Bacteroides. Genus Ruminococcaceae_UCG-008 was positively correlated with GABA and BDNF levels in the hippocampus; genus Lactobacillus had a positive correlation with 5-HT; and genus Bacteroides had negative correlations with 5-HT, BDNF, and NE. In addition, Semen Sojae Praeparatum considerably decreased the concentration of short-chain fatty acids (SCFAs). These results indicated that Semen Sojae Praeparatum fermented by Rhizopus chinensis 12 and Bacillus sp. DU-106 alleviated the neurotransmitter levels and structural changes in the neuronal morphology of the hippocampus associated with the modulation of gut microbiota and SCFAs. Therefore, this study confirmed that Semen Sojae Praeparatum could alter depression and provide a theoretical basis for the investigation of the relationship between the microbiota-gut-brain axis and antidepressant.