Comparative Analysis of Lower Genital Tract Microbiome Between PCOS and Healthy Women

Abstract

Women with polycystic ovarian syndrome (PCOS) often have a history of infertility and poor pregnancy outcome. The character of the lower genital tract (LGT) microbiome of these patients is still unknown. We collected both vaginal and cervical canal swabs from 47 PCOS patients (diagnosed by the Rotterdam Criteria) and 50 healthy reproductive-aged controls in this study. Variable regions 3-4 (V3-4) were sequenced and analyzed. Operational taxonomic unit (OTU) abundance was noted for all samples. Taxa that discriminated between PCOS and healthy women was calculated by linear discriminant analysis effect size (LEFSe). Results from 97 paired vaginal and cervical canal samples collected from 97 women [mean age 30 (±4 years)] were available for analysis. Using the Rotterdam Criteria, 47 women were diagnosed with PCOS (PCOS, n = 47; control, n = 50). There was no significant difference between cervical canal microbiome and vaginal microbiome from the same individual, however, Lactobacillus spp. was less abundant in both vaginal and cervical canal microbiome of PCOS patients. Several non-Lactobacillus taxa including Gardnerella_vaginalis_00703mash, Prevotella_9_other, and Mycoplasma hominis, were more abundant in the LGT microbiota of PCOS patients. There is a difference between the microorganism in the LGT of patients with PCOS and healthy reproductive-aged women.

Keywords: Gardnerella; Lactobacillus; PCOS; lower genital tract (LGT); microbiome.

FIGURE 1

Composition of LGT microbiomes from healthy controls and PCOS patients. General taxa (genus level) composition of vagina (A) and cervical canal (B) of PCOS patients (n = 47) and healthy controls (n = 50) are presented, and the main 30 genera are listed. Grouped OTU abundance of vagina (C) and cervical canal (D) microbiome from PCOS and healthy women are also listed.

FIGURE 2

Biodiversity of the LGT microbiomes is increased in PCOS patients. Box plots of the biodiversity in vagina and cervical canal samples from healthy women (n = 50), and women diagnosed with PCOS using the Rotterdam criteria (n = 47) were presented. α-Diversity was presented by Faith’s PD index: vagina (A) and cervical canal (B); β-diversity of microbiome was performed using PCoA analysis: vagina (C) and cervical canal (D).

FIGURE 3

Taxa differed between PCOS and healthy women. 16S-Derived microbial taxa abundance were compared between healthy controls and PCOS patients in both vagina (A) and cervical canal (B) as analyzed by LEfSe projected as a cladogram and by LDA score (>2). Relative abundance of Lactobacillus in both vagina (C) and cervical canal (D) of PCOS women was significantly reduced compared with the healthy controls, as measured by Wilcoxon test.

FIGURE 4

Functional analysis of microbial composition in a total of 97 women’s LGT. KEGG pathways were predicted by the relative abundance of microorganisms in 97 women’s LGT. The dysregulated KEGG pathways in the vagina and cervical canal were selected by Wilcoxon rank-sum test and visualized as a heatmap in panels (A,B), respectively. The pathways and samples were clustered by unsupervised hierarchical clustering.