Clinical Manifestations of Polycystic Ovary Syndrome and Associations With the Vaginal Microbiome: A Cross-Sectional Based Exploratory Study

Abstract

BackgroundPrevious studies suggest that the vaginal microbiome is associated with polycystic ovary syndrome (PCOS). However, the clinical manifestations of PCOS are heterogeneous. Whether the vaginal microbiome is related with different clinical symptoms was unknown.Materials and MethodsIn this cross-sectional study, 89 female patients with PCOS admitted to Zhongda Hospital (Nanjing, China) were included. Basic demographic information, health-related behaviors, clinical manifestations and sex hormone levels were comprehensively recorded for all patients. Vaginal swabs were acquired for microbiota sequencing of the V3–V4 region of the 16S rRNA gene.ResultsThe prevalence of bacterial vaginitis and vulvovaginal candidiasis was 15.7% and 13.5%, respectively, within the PCOS patients, which were the most important factors affecting the vaginal microbiome (permutational multivariate analysis of variance test, R2 = 0.108, P = 0.001). The vaginal microbiome was associated with specific clinical manifestations of PCOS, including acanthosis nigricans, intermenstrual bleeding, pregnancy history, testosterone level and anti-müllerian hormone level, with P values < 0.05. The abundance of Lactobacillus crispatus was higher (P = 0.010) while that of Lactobacillus iners was lower (P = 0.036) among PCOS patients with elevated testosterone levels. Other potential bacterial biomarkers were not statistically significant after adjusting for confounding factors. No evidence of associations of other common manifestations of PCOS, such as obesity and acne, with the vaginal microbiome was obtained.ConclusionVaginal bacterial species among PCOS patients with variable clinical manifestations, especially differences in testosterone levels, are distinct. Further studies are essential to investigate the microbiota and molecular mechanisms underpinning this disease.

Interplay between PCOS and microbiome: The road less travelled

“…Additionally, LPS and Vaginolysin which is a virulence factor secreted by membrane vesicles of Gardnerella vaginalis 53 can bind to the nod‐like receptor, generating the NLRP3 inflammasome complex, which can trigger the release of IL‐1β and IL‐18, causing inflammation 52 . Moreover, a study found a link between high AMH levels and vaginal Mycoplasma colonisation in women with PCOS and AMH which is a glycoprotein hormone that plays a vital role in growth differentiation and folliculogenesis and elevated amount of which can lead to anovulation, therefore this could be a possible link underlying microbiota influenced PCOS‐related clinical presentation 54,55 …”

“…52 Moreover, a study found a link between high AMH levels and vaginal Mycoplasma colonisation in women with PCOS and AMH which is a glycoprotein hormone that plays a vital role in growth differentiation and folliculogenesis and elevated amount of which can lead to anovulation, therefore this could be a possible link underlying microbiota influenced PCOS-related clinical presentation. 54,55 Since ovulation is identified as a cytokine-regulated inflammatory pathway, and several member of the Toll-like receptor (TLR) are pre-sented on granulose cells and cumulus cells of ovulating follicles, inflammation which can induce expression of certain genes and may influence ovarian surface epithelial cells at the time of ovulation and any abnormality in the levels of these inflammatory factors can lead to infertility due to the altered gene expression patterns in ovarian cells [53][54][55] which is evidence suggesting microbiota can be correlated to clinical manifestations of PCOS, such as menstrual irregularities. While there is a little direct indication for the pathogenic bacteria related dysfunction in the ovary in case of PCOS, the microbiota's implication on the female genital system influencing PCOS is worth exploring and thus, additional research into microbiome and molecular pathways underlying with PCOS are required for a potential conclusion of the underpinning mechanism behind the correlation of microbiota and ovarian axis.…”

The associations between low abundance of Mycoplasma hominis and female fecundability: a pregnancy-planning cohort study

“…The swabs were transferred to a − 80 °C refrigerator, and saved for bacterial nucleic acid extraction. Following the standard procedures in our laboratory, [ 14 ] swabs were eluted in 2 ml PBS, and TIANamp Bacteria DNA Kits (Tiangen Biochemical Technology, Beijing, China) were used to extract and purify DNA. The concentrations of DNA were measured through Nanodrop one (Thermo Scientific Co.,Ltd., MA, USA).…”

The association between the pre-pregnancy vaginal microbiome and time-to-pregnancy: a Chinese pregnancy-planning cohort study

“…Quantitative real-time polymerase chain reaction (qPCR) was used to measure the absolute loads of specific vaginal bacteria, including L. crispatus, L. gasseri, L. iners, Gardnerella vaginalis (G. vaginalis), and Fannyhessea vaginae (F. vaginae, also called Atopobium vaginae). We used specific primers that had been verified by previous studies (further details are given in Additional file 2: Table S1 [18][19][20][21]). We used the NCBI Blast database to predict the amplified products, and specific plasmids were synthesized by Sangon Biotech Company (Shanghai, China).…”