For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis.
Colonization of the endometrium by pathogenic bacteria, ascending from the lower female reproductive tract (FRT), is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions in vitro, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue including cell differentiation, junctional complexes/desmosomes, microvilli, membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with polyinosinic-polycytidylic acid (poly(I:C)) and flagellin, but not with synthetic lipoprotein (FSL-1) or lipopolysaccharide (LPS), significantly induced proinflammatory mediators in a dose dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria: Lactobacillus crispatus, Gardnerella vaginalis and Neisseria gonorrhoeae All vaginal microbiota and N. gonorrhoeae efficiently colonized the 3-D surface localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic N. gonorrhoeae significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells relative to other bacteria tested. This latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of 3-D EEC model to study N. gonorrhoeae pathogenesis using a well-characterized ΔpilT mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.