Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice

Abstract

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1β and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis. Video Abstract.

Keywords: Bacterial vaginosis; Lactic acid bacteria; Synthetic bacterial consortia transplantation; Vaginal microbiota.

Fig. 1

The bacterial burdens in vaginal lavage fluids were assessed longitudinally on days 4, 6, 8, and 21; results are shown as means ± standard error of the mean

Fig. 2

Tissues were stained with hematoxylin-eosin and sections were evaluated by a Pannoramic MIDI digital section scanner. a CON, normal control mice. b GVI, GV-infected mice. c SBCT, synthetic bacterial consortia treatment for mice. d VMT, vaginal microbiota transplantation treatment for mice, magnification × 100

Fig. 3

Levels of IL-1β, IL-8, and IL-10 in the serum of mice in different groups. a IL-1β, interleukin-1β. b IL-8, interleukin-8. c IL-10, interleukin-10. Results are shown as means ± standard error of mean. *P < 0.05 vs. GVI group

Fig. 4

Expression of TNF-α, iNOS and COX-2 genes in the vaginal tissues of mice. Data are presented as the means ± standard error of mean obtained from three independent experiments. a TNF-α, tumor necrosis factor-α. b iNOS, inducible nitric oxide synthase. c COX-2, cyclooxygenase 2. #P < 0.05 vs. normal control group; *P < 0.05 vs. GVI group

Fig. 5

Expression of helper T cell transcription factors in the vaginas of mice. a IL-17, interleukin-17. b FOXP3, Forkhead Box Protein P3. Data are presented as the means ± standard error of the mean of three independent experiments. #P < 0.05 vs. normal control group; *P < 0.05 vs. GVI group

Fig. 6

Evaluation of the vaginal microbiota in mice with vaginal microbiota dysbiosis using high-throughput sequencing: a Chao 1 index; b Shannon index; c Scalar Venn representation

Fig. 7

Principal coordinates analysis (PCoA) of the dissimilarity between the microbial samples: a CON and GVI group; b SBCT and GVI group; c VMT and GVI group

Fig. 8

Comparison of the relative abundance at genus level by LEfSe analysis: a CON and GVI groups; b SBCT and GVI groups; c VMT and GVI groups

Fig. 9

The relative abundance of the dominant bacteria of the vaginal microbiome at the genus level. *P < 0.05 vs. GVI group

Fig. 10

Clusters of orthologous groups (COG)-predicted functional classification with different treatments. a CON and GVI groups. b SBCT and GVI groups;. c VMT and GVI groups

Fig. 11

Experimental scheme for the treatment of vaginal dysbiosis by synthetic bacterial consortia transplantation and vaginal microbiota transplantation