An Updated Conceptual Model on the Pathogenesis of Bacterial Vaginosis

Abstract

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.

Gardnerella vaginalis Enhances Atopobium vaginae Viability in an in vitro Model

“…Despite the evidences suggesting that Gardnerella spp. might be the initial colonizer, establishing early biofilm structures to which A. vaginae can attach (Swidsinski et al, 2005;Castro et al, 2019;Muzny et al, 2019), there is a lack of studies addressing why A. vaginae is almost always accompanied by Gardnerella spp. in the vaginal microbiota (Verhelst et al, 2004;Bradshaw et al, 2006;Menard et al, 2010;Hardy et al, 2015Hardy et al, , 2016.…”

“…Bacterial vaginosis (BV) is the most prevalent bacterial vaginal infection in women of reproductive age (Jung et al, 2017;van de Wijgert and Jespers, 2017;Rosca et al, 2019). BV is characterized by a change in the microbial composition of the vaginal ecosystem where the prevailing Lactobacillus spp., associated with an optimal vaginal microbiota, are outnumbered by other microorganisms, including species of the genus Gardnerella and Atopobium vaginae (Ferris et al, 2004;Verhelst et al, 2004;dos Santos Santiago et al, 2012;Jung et al, 2017;Muzny et al, 2019). Noteworthy, the involvement of A. vaginae in BV rarely occurs in the absence of Gardnerella (Bradshaw et al, 2006;Hardy et al, 2015Hardy et al, , 2016.…”

Gardnerella vaginalis as a Cause of Bacterial Vaginosis: Appraisal of the Evidence From in vivo Models

“…Despite Gardner and Dukes early assertions that Gardnerella was the sole causative agent of BV, this is not a universally accepted hypothesis (Hickey and Forney, 2014;Schwebke et al, 2014a,b). Another hypothesis is that multiple species of bacteria are needed to generate the features and complications that have been associated with the condition (Muzny et al, 2019a). There is also evidence, however, that G. vaginalis may still have a role in the development of features that it does not directly cause, and may do so by impacting the abundance or pathogenesis of other organisms.…”

“…While some believe that G. vaginalis may be a sole causal contributor to BV (Schwebke et al, 2014b), others have been skeptical of this and consider G. vaginalis to be one of many within the BV consortium (Hickey and Forney, 2014;Schwebke et al, 2014a). Recently, a more complex model has been proposed, taking into account recent efforts to build animal models for BV and arguing that relationships between multiple microbes, including G. vaginalis, may underpin the condition (Muzny et al, 2019a).…”

Growth Forms of Gardnerella spp. and Lactobacillus spp. on Vaginal Cells

“…and an overgrowth of vaginal anaerobic bacteria (Hillier et al, 1993;Fredricks et al, 2005;Ravel et al, 2013). Although the exact pathogenesis of BV remains unknown, two main hypotheses are currently in debate to explain the BV etiology-that BV is triggered by the initial establishment of the "key bacteria" such as virulent strains of Gardnerella spp., Prevotella bivia, Atopobium vaginae and Megasphaera type 1; or it is caused by the sexual introduction of the polymicrobial community that predominantly consists of the above-mentioned "key bacteria" (Srinivasan and Fredricks, 2008;Muzny and Schwebke, 2013;Muzny et al, 2018Muzny et al, , 2019. Gardnerella spp.…”