Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis

Abstract

Purpose of review: The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host-vaginal microbiota interactions in bacterial vaginosis pathogenesis.

Recent findings: Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host-immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes.

Summary: Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.

Figure 1.. Depiction of putative model for the establishment of BV and immunologic/physiological changes related to host-microbe interactions.

A. In a healthy state the vaginal microbiome is dominated by Lactobacillus species. Lactobacilli produce lactic acid, which lowers the vaginal pH and protects against invading pathogens and pathobionts. Epithelial cells constitutively produce low levels of antimicrobial peptides (e.g. SLPI) and cytokines. Additionally, epithelial cells and immune cells contribute to homeostasis by producing anti-inflammatory cytokines (e.g. IL-1RA). B. Vaginal dysbiosis begins with initial colonization with the facultative anaerobe, Gardnerella vaginalis, usually following a sexual exposure. G. vaginalis colonizes the vaginal epithelial cells, replaces lactobacilli, and provides scaffolds for biofilm formation. Following G. vaginalis colonization, the strict anaerobe, Prevotella bivia, is recruited to the biofilm. G. vaginalis and P. bivia support each other’s growth through ammonia and amino acid metabolism. Both G. vaginalis and P. bivia are capable of producing enzymes, e. g. sialidase, which may contribute to mucus degradation and barrier disruption. No overt inflammation is observed, which suggest that these bacterial species are able to evade host immune response through unknown mechanisms. C. Other secondary colonizers, e.g. Atopobium vaginae and Sneathia spp., are recruited to the biofilm. At this stage, exfoliation of epithelial cells coated with the polymicrobial biofilm occurs. These “clue cells” can be detected in wet mounts of vaginal fluid and are included in the Amsel criteria. Production of biogenic amines and other metabolites produced by BV-associated bacteria contribute to elevated vaginal pH and BV symptoms such as fishy odor. Epithelial cells and recruited immune cells produce pro-inflammatory cytokines and chemokines, which could lead to genital inflammation.