Vaginal Microbiome and Epithelial Gene Array in Post-Menopausal Women with Moderate to Severe Dryness

Abstract

After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to the loss of estrogen. An understudied aspect of vaginal health in women who experience dryness due to atrophy is the role of the resident microbes. It is known that the microbiota has an important role in healthy vaginal homeostasis, including maintaining the pH balance and excluding pathogens. The objectives of this study were twofold: first to identify the microbiome of post-menopausal women with and without vaginal dryness and symptoms of atrophy; and secondly to examine any differences in epithelial gene expression associated with atrophy. The vaginal microbiome of 32 post-menopausal women was profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Sixteen subjects were selected for follow-up sampling every two weeks for 10 weeks. In addition, 10 epithelial RNA samples (6 healthy and 4 experiencing vaginal dryness) were acquired for gene expression analysis by Affymetrix Human Gene array. The microbiota abundance profiles were relatively stable over 10 weeks compared to previously published data on premenopausal women. There was an inverse correlation between Lactobacillus ratio and dryness and an increased bacterial diversity in women experiencing moderate to severe vaginal dryness. In healthy participants, Lactobacillus iners and L. crispatus were generally the most abundant, countering the long-held view that lactobacilli are absent or depleted in menopause. Vaginal dryness and atrophy were associated with down-regulation of human genes involved in maintenance of epithelial structure and barrier function, while those associated with inflammation were up-regulated consistent with the adverse clinical presentation.

The primate vaginal microbiome: Comparative context and implications for human health and disease

“…Data from vervets, baboons, and mangabeys (Street et al, 1983;Johnson et al, 1984) as well as rabbits, mice and rats (Linhares et al, 2011) also indicate that the vaginal environment of these species is characterized by a higher, near neutral pH. Consequently, the low Lactobacillus loads, low lactic acid and high pH characteristic of NHPs resemble human vaginal dysbiosis (microbial imbalances), BV, or postmenopausal changes (e.g., Sneathia, Anaerococcus, Prevotella, Gardnerella, Gemella, Facklamia, Peptoniphilus) (Spear et al, 2010;Hummelen et al, 2011;Yildirim et al, 2011).…”

High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

“…It is proposed that the lactic acid maintains an acid pH which helps to protect the vaginal tissues from colonisation by potential uropathogens including E. coli . Postmenopausal women are characterised by reduced oestrogen levels and those suffering rUTIs typically show a vaginal pH above 4.5,12 suggesting that the reduced oestrogen levels impact negatively on Lactobacilli growth, which adversely affects the vaginal microbiome 13, 14, 15. In support of a role for oestrogen in the innate defence of the urogenital tract, topical, but not oral oestrogen treatments have proven successful in reducing infections with these effects mediated through the vaginal commensal populations and the urogenital innate defences 16, 17, 18, 19.…”

Persistence of Lactobacilli in Postmenopausal Women - A Double-Blind, Randomized, Pilot Study

“…Fisher's exact test was used lactobacilli at the strain level. The frequencies of colonization of the vagina by lactobacilli decrease after menopause and different results have been reported with different methods [9,14] .…”

“…The lactobacilli are considered to protect the genital health by competitive exclusion of genitourinary pathogens, co-aggregation with uropathogenic bacteria, formation of a biofilm and production of inhibitory compounds such as lactic acid and other metabolites [6,7,9,13,14].…”