| Objective To explore the effect of Zishen Shugan decoction on the intestinal flora of rats with perimenopausal depression based on 16S rDNA high-throughput sequencing. Methods Eighteen SPF female SD rats were selected and randomly divided into sham operation group (Sham, n = 3), model control group (Model, n = 3), low-dose Zishen Shugan Prescription group (Low, n = 3), middle-dose Zishen Shugan Prescription group (Middle, n = 3), Zishen Shugan Prescription high dose group (High, n = 3) and positive control group (Positive, n = 3). Except for the Sham group, the rest of the groups underwent ovarian ablation surgery, followed by chronic unpredictable stimulation to establish models. At the same time, the Sham group and Model group were given intragastric administration of normal saline; the Positive group were given intragastric administration of fluoxetine hydrochloride and estradiol valerate suspension; the Low group, Middle group and High group were fed with Zishen Shugan decoction respectively. After continuous administration, the richness and diversity of intestinal flora were detected by 16S rDNA sequencing technology. Results At the phylum level, Firmicutes, Bacteroidetes, and Proteobacteria were the most abundant flora in the intestinal of perimenopausal depressed rats, and at the genus level, Lachnospiraceae_NK4A136_group, uncultured_Bacteroidales_bacterium, and Alistipes had the highest abundance. Compared with the Sham group, the abundances of Firmicutes, Epsilonbacteraeota, and Chloroflexi in the Model group were lower than those in the Sham group (P < 0.05). After intragastric administration of Zishen Shugan Recipe, the abundance of Firmicutes, Epsilonproteobacteria, and Chloroflexi was improved in the low, medium (P < 0.05), and high (P < 0.05) dose groups respectively. Functional annotation analysis showed that after intragastric administration of middle dose of Zishen Shugan prescription, the levels of photosynthesis-antenna protein (P < 0.01) and Staphylococcus aureus infection (P < 0.05) related pathways were up-regulated, and the levels of styrene degradation (P < 0.05) and geraniol degradation (P < 0.05) were down-regulated, while high-dose intragastric administration of geraniol degradation was up-regulated (P < 0.05). Conclusion Changes in the structure and function of intestinal flora are important factors leading to perimenopausal depression. Zishen Shugan decoction can improve the disorder of intestinal flora to a certain extent and optimize the composition of intestinal flora. |