Dysbiosis in the Vaginal Microbiota May be Associated With the Development of Localized Provoked Vulvodynia (LPV)
Trial Snapshot
- Phase
- Phase 3
- Enrollment
- 70
- Primary Endpoint
- Change in vaginal microbiome composition of women with localized provoked vulvodynia following three months of low oxalate diet
Study Overview
Brief Summary
Currently, the pathogenesis of Localized Provoked Vulvodynia (LPV) has not been elucidated. Few observations may point to involvement of the microbiome: the association of LPV with preceding chronic recurrent candidiasis, and the reports of the beneficial effect of a diet avoiding oxalate on Vulvodynia.
Studies in the new field of microbiome research focus on the composition of overall microorganisms in our body and their impacts on our health. Changes in the composition of the vaginal microbiota (dysbiosis) have been linked with different health and disease states. We have also shown recently that women can be divided into 2 groups according to the composition of their vaginal microbiome.
The proposed study will compare the vaginal microbiome of women with severe LPV, not treated by diet and otherwise healthy, to women without LPV (we will also compare our results to the NIH HMP data). Vaginal pH and date of menstrual cycle will be checked. We propose that dysbiosis in the vaginal microbiota may trigger the development of LPV.
Detailed Description
Vulvodynia - vulvar pain. The exact etiology has not been elucidated yet, and therapy is often unsatisfactory. Two main types of Vulvodynia exist, with the far more common type being Localized provoked vulvodynia (LPV), also known as Vestibulodynia, and in the past - Vestibulitis. This study will concentrate on this common disorder which affects young women, whose quality of life deteriorate significantly by the inability to experience vaginal sex.
The vaginal microbiome The new field of microbiome research focuses on the composition of overall microorganisms in the human body and their impacts on our human health. Amazingly, the number of microbial cells within our body is 10 times greater than the sum of all our human somatic and germ cells, and they carry 150 times more genetic information than our own. Changes in the composition of the vaginal microbiota (dysbiosis) have been linked with different health and disease states.
The vagina is colonized with around 108-109 bacteria/mL vaginal fluid which is comparable to the small intestine. Recently, the NIH Human Microbiome Project characterized the bacterial communities across the human body and found that the vagina harbors low complexity bacterial communities. These communities had the lowest alpha diversity (within sample diversity) among the different body sites and low beta diversity (between sample diversity) at the genus level. This diversity was high at the species level due to distinct Lactobacillus spp. The communities were sampled at the sub sites that included the posterior fornix, mid vagina and the vaginal introitus. There was little distinction between the three sites hence we will focus on posterior fornix. The vaginal communities of healthy women, have also been repeatedly observed to occupy one of five states, four dominated by Lactobacillus spp. and one by higher overall microbial diversity. Shifts between the community structures within individuals (dysbiosis) are associated with disease states so it would be interesting to study whether women with LPV belong to a different enterotype than healthy women.
The vaginal microbial communities have been shown to change during different stages in a woman's life and to influence pregnancy. As early as 1930, Cruickshank and Baird described changes in the vaginal bacterial communities that occurred between the 5th and 7th month of pregnancy.
In 2010 a study was undertaken among Amerindian women to examine the microbial vaginal signature at term in relation to delivery mode (n=9). Variability in vaginal taxa was noted between subjects particularly for Lactobacillus species. Metagenomic analysis of the vaginal microbiome in a cross-sectional study of 24 healthy pregnant women and 60 non-pregnant controls at three vaginal sites (introitus, posterior fornix and midvagina) found the richness and diversity of the vaginal microbiome to be reduced in pregnancy in ways that did not appear to be driven by BMI, race or ethnicity . As pregnancy progressed and as proximity to the uterus increased, less diversity and richness were noted. Lactobacillus species were enriched in pregnancy, which the authors postulated may be biologically significant as lactic acid bacteria produce bacteriocins that may reduce the risk of ascending infections. It has also been proposed that the vaginal microbiota has the potential to influence the conception process by influencing the local production of proinflammatory cytokines which in turn impact the survival rate and motility of sperm cells.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy women, aged 18-50 years, meet Friedrich's first two criteria for vulvar Vestibulitis syndrome, suffer from levels II or III dyspareunia according to Marinoff
Exclusion Criteria
- •Women suffering from generalized Vulvodynia (constant vulvar pain - unrelated to provocation), pregnant or lactating. Women will also be excluded from the study if they were have any medical condition, acute or chronic, or anticipated not being available for the one month follow up visit, have received antibiotics during the month preceding the study.
Outcomes
Primary Outcomes
Change in vaginal microbiome composition of women with localized provoked vulvodynia following three months of low oxalate diet
Time Frame: Within one week after three months of low oxalate diet
The microbiome components will be examined before and after the diet by characterization of the genomic components of the bacterial communities
Secondary Outcomes
- Level of dyspareunia following three months of low oxalate diet in women with localized provoked vulvodynia(Within one week after three months of low oxalate diet)
Investigators
Prof. Jacob Bornstein
Principal Investigator
Western Galilee Hospital-Nahariya
