Mechanisms of Wandai Decoction in Improving Vaginal Flora of Vulvovaginal Candidiasis of the Spleen Deficiency and Excessive Dampness Type: A Study Based on Metagenomics and Metabolomics

Abstract

To explore the mechanism by which Wandai Decoction prevents and treats vulvovaginal candidiasis (VVC) of the spleen deficiency and excessive dampness type and restores the vaginal flora structure, and to identify the potential metabolic pathways involved using metagenomics and metabolomics.

Methods  Twenty VVC patients who met the inclusion criteria were randomly assigned to a Wandai Decoction group and a fluconazole group (n = 10 in each group). Subjects in the fluconazole group were given a single oral dose of 150 mg fluconazole, while those in the Wandai Decoction group took the Wandai Decoction orally for 14 days. The vulvovaginal signs and symptoms (VSS) scores of both patient groups were evaluated before and after treatment. Vaginal secretions were collected before and after treatment. The Illumina sequencing and the liquid chromatography with tandem mass spectrometry (LC-MS/MS) platform were used to conduct metagenomic and metabolomics analyses of the vaginal secretions, respectively.

Results  The VSS score results showed that the VSS scores of both groups decreased after treatment compared with those before treatment (P < 0.01), and there was no statistically significant difference in the VSS scores between the two groups after treatment. Metagenomics results showed that, after treatment, the vaginal microbial communities in the Wandai Decoction group were of CST Ⅱ and Ⅴ types (predominated by Lactobacillus gasseri and Lactobacillus jensenii), while those in the fluconazole group were Lactobacillus_intestinalis and Streptococcus_sp._oral_taxon_431. KEGG functional enrichment analysis results showed that, in terms of the cell cycle and meiosis functions of Candida albicans, statistically significant differences between the Wandai Decoction and fluconazole groups were observed (P < 0.05). Metabolomic analysis identified 120 differential metabolites between the two groups after treatment. The results of KEGG metabolic pathway enrichment analysis of differential metabolites showed that the Wandai Decoction might be significantly superior to fluconazole in improving local vaginal metabolic pathways of α-linolenic acid, glycerophospholipid metabolism, pentose and glucuronic acid interconversion, and arachidonic acid.

Conclusion  The Wandai Decoction can improve the vaginal flora of VVC patients. It may be superior to fluconazole in the signaling pathways of the cell cycle and meiosis. The improvement of the vaginal flora by the Wandai Decoction may be associated with its effect on metabolic pathways of glycerophospholipid metabolism, pentose and glucuronic acid interconversion, and others in the vagina.

Keywords: Wandai Decoction, Vulvovaginal candidiasis, Vaginal flora, Metagenomics, Metabolomics