How Lactobacilli dominate the vaginal microbiota, thereby protecting against polymicrobial communities and other vaginal infections

[摘要] Lactobacilli colonize the human vagina and acidify it with lactic acid. In this highly acidic environment Lactobacilli manage to achieve a sparse, but near monomicrobial community, in which very few other species of bacteria are present. Despite the acidity of the vaginal environment, I have found that vaginal Lactobacilli grow optimally at a near neutral pH in cervicovaginal fluid (CVF) or culture media. Even when directly exposed to the acidity of the vagina, however, I observed ex vivo that the Lactobacilli are still growing and producing lactic acid at a slow rate. Women who do not have a monomicrobial community of Lactobacilli, have a polymicrobial community made up of many different gram-negative bacteria. Using ex vivo conditions I determined that vaginal lactic acid was sufficient to inactivate bacteria from the polymicrobial vaginal communities, precluding the necessity of peroxide production or bacteriocins, which have been previously suggested. Therefore, by maintaining high vaginal acidity, even at a slowed growth rate, Lactobacilli can protect the vagina against other communities of bacteria. Mild acidification beyond the stable pH attained by Lactobacilli in vivo, however, inactivated the Lactobacilli themselves. For the vaginal pH to remain stable and above what is fatal to the Lactobacilli, it requires a model in which lactic acid is lost from the vagina at the same rate as which the bacteria produce it, and where the rate the bacteria grow and adhere to the epithelium matches the rate of vaginal epithelial cell shedding. The majority of women worldwide have a polymicrobial community of vaginal bacteria, putting them at a higher risk for the acquisition and transmission of sexually transmitted infections, and poor birth outcome. For unknown reasons this risk also extends to women with specific Lactobacilli spp. By measuring the vaginal acidity across different community state types I found that the higher risk Lactobacilli community (CST III-INERS) was correlated with less vaginal acidity. Therefore, the difference in risk between different bacterial communities is likely due to a difference in vaginal acidity. Vaginal acidity may inactivate pathogens outright, or protect a Lactobacilli dominated community by inactivating bacteria from polymicrobial vaginal communities. Even women with high vaginal acidity, however, have been observed to occasionally transition to a polymicrobial community. This suggests that other mechanisms must exist to determine which bacterial communities can remain in the vagina. Few studies have attempted to determine if the mucosal immune system plays a role in maintenance of vaginal bacteria communities, and of these studies none of have reported on host-antibody coating of vaginal bacteria, despite the important role it plays in the maintenance of gut bacteria. Using both microscopy and flow cytometry approaches I report antibody coating of vaginal Lactobacilli. Each method revealed extensive coating with IgG and IgA. A subset of the cultured bacteria from a CVF sample could be recoated with host antibodies from the CVF supernatant, suggesting some antibody specificity, and a potential role for the mucosal immune system in the regulation of vaginal bacterial communities.

[发布机构] Johns Hopkins University

[效力级别] Humans

[关键词] Vagina;Humans;Lactobacillus;Lactic Acid;Bacterial Vaginosis;Sexually Transmitted Diseases;Microbiota;Cervicovaginal Fluid;Microscopy;Mucous Membrane;Immune System;Flow Cytometry;Biology