Anti-depressive effects of Xiaoyaosan, Shugan and Jianpi herbal treatments: role on the gut microbiome of CUMS rats

Abstract Background : Xiaoyaosan (XYS), a classic traditional Chinese medicine (TCM) prescription that contained eight Chinese herbs, has been used for treating depression for thousands of years. Yet, the underlying mechanisms are still unclear, which need to be investigated from various perspectives. Disassembling a prescription is one of the effective approaches to study the effects and mechanisms of TCM prescriptions. By disassembling the prescription, we can find effective combinations of individual herbs to simplify the scale of a given prescription. Accordingly, herein, XYS was disassembled into Shugan and Jianpi groups. Purpose : This study was aimed to explore the anti-depressive effects of XYS and its disassembled groups on the digestive system functions and the cecal microbiota of rats. Methods : XYS was divided into two efficacy groups, i.e., the Shugan (SG) and the Jianpi (JP) groups. A depression model was applied by using the chronic unpredictable mild stress (CUMS) method. Various classic behavioral tests were performed to assess the anti-depressive effects of the XYS, the SG, and the JP. Afterward, the effects of the three groups on the digestive system functions and the cecum microbiota of depression rats were evaluated. On top of this, correlation analyses between behavioral and digestive system function indexes and cecum microbiota were conducted. Results : The XYS, the SG, and the JP had significant callback effects on depressive behaviors and gastrointestinal dysfunctions in CUMS rats. The compositions of the gut bacterial community were variable among the five groups. The community composition of the SG was the most similar to that of NC, followed by the XYS and the JP. At phylum, family, and genus levels, 31 potential microbial biomarkers associated with CUMS were identified. Twenty biomarkers were significantly reversed by the SG while 16 and 11 biomarkers were reversed by the XYS and the JP, respectively. The results of degrees of regulatory effects showed that the SG had the highest efficacy index (EI) than the XYS and the JP. Conclusion : Regarding the regulation of cecal microbiota of depression rats, the SG treatment was better than XYS and JP. Therefore, SG could be used individually for the clinical treatment of depression, especially in patients with gastrointestinal and gut microbiota disorders.