The Dwindling Microbiota of Aerobic Vaginitis, an Inflammatory State Enriched in Pathobionts with Limited TLR Stimulation

Abstract

While bacterial vaginosis (BV) is a well-known type of vaginal dysbiosis, aerobic vaginitis (AV) is an inflammatory condition that remains understudied and under-recognised. It predisposes women to serious complications including urogenital infections and pregnancy problems. Here, we investigated the bacterial community in AV to explore its possible role in AV pathogenesis. We collected vaginal lavage fluid samples of women (n = 58) classified by wet-mount microscopy as suffering from AV or BV and included an asymptomatic reference group without signs of AV or BV. AV samples showed reduced absolute abundances of bacteria in general and specifically of lactobacilli by qPCR, but 16S rRNA gene sequencing and amplicon sequence variant analysis revealed that Lactobacillus remained the dominant taxon in 25% of the AV samples studied. The other AV samples showed high relative abundances of Streptococcus agalactiae and, unexpectedly, the anaerobes Gardnerella vaginalis and Prevotella bivia in more than half of the AV samples studied. Yet, despite increased relative abundance of these potential pathogens or pathobionts in the AV bacterial communities, the AV samples only slightly stimulated Toll-like receptor 4 and showed reduced activation of Toll-like receptor 2/6, receptors of two pathways central to mucosal immunity. Our findings indicate that the reduced total bacterial abundance with associated enrichment in certain pathobionts in AV might be mainly a consequence of the inflammatory conditions and/or altered hormonal regulation rather than bacteria being a major cause of the inflammation.

Aerobic Vaginitis—Underestimated Risk Factor for Cervical Intraepithelial Neoplasia

“…A recent study showed that increased numbers of Prevotella bivia and P. disiens could help to predict CIN2+ in HR-HPV-positive women [ 44 ]. Interestingly, recently P. bivia was also found to be one of the most important representatives in the microbiome of AV, alongside Streptococcus agalactiae [ 45 ].…”

The Association between Vaginal Dysbiosis and Reproductive Outcomes in Sub-Fertile Women Undergoing IVF-Treatment: A Systematic PRISMA Review and Meta-Analysis

“…NGS provides a relative abundance measure, which may underestimate the presence of some bacterial species, due to e.g., high total concentrations of other bacterial species. For example, L. iners has a 15-fold higher concentration than L. crispatus by qPCR [ 29 ], and another study using genus specific primers did not observe statistical difference in the total number of lactobacilli comparing normal vaginal microbiota to BV [ 56 ]. This could result in a microbiota, which by NGS would have a relative abundance skewed by a high total abundance of e.g., L. iners which may “cover-up” VD bacteria such as Gardnerella spp.…”

“…may be underestimated by relative 16S rRNA gene sequencing [ 53 ]. Typically, BV has a significantly higher total bacterial load compared to normal vaginal microbiota [ 56 ]. For this reason, it is important to acknowledge that underestimated bacteria by relative abundances may still have a physiological effect.…”

Recent Advances in Presentation, Diagnosis and Treatment for Mixed Vaginitis

“…DIV/AV: The diagnosis of DIV/AV should be based on a combination of clinical features and microscopic findings ( Oerlemans et al., 2020 ). The clinical features are as follows: vulvar erythema; vulvar swelling; thinning of the vaginal mucosa; vaginal congestion; scattered bleeding points; and yellow-colored vaginal secretion, increased discharge or pruritus.…”