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Am J Obstet Gynecol. 2020 Nov 25:S0002-9378(20)31331-4. doi: 10.1016/j.ajog.2020.11.032. Online ahead of print.
BACKGROUND: Group B Streptococcus (GBS) is a common vaginal bacterium and leading cause of invasive fetoplacental infections. GBS in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a “dysbiotic” polymicrobial and/or Lactobacillus-depleted vaginal microbiota are more likely to harbor GBS. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse models of GBS and G. vaginalis colonization have been reported but the two have not, to our knowledge, been studied together. The overarching idea driving this study is that certain members of the dysbiotic vaginal microbiota, such as G. vaginalis, may directly contribute to the increased rate of GBS vaginal colonization observed in women with vaginal dysbiosis.
OBJECTIVE: We used a mouse model to test the hypothesis that vaginal exposure to G. vaginalis may facilitate colonization and/or invasive infection of the upper reproductive tract by GBS during pregnancy.
STUDY DESIGN: Timed-pregnant mice were generated using an allogeneic mating strategy with BALBc males and C57Bl/6 females. Dams were vaginally inoculated at gestational day (E)14 with GBS-alone (using a 10-fold lower dose than previously reported models) or co-inoculated with GBS and G. vaginalis. Bacterial titers were enumerated in vaginal, uterine horn and placental tissues at E17. The presence (Fisher’s exact tests) and levels (Mann-Whitney tests) of bacterial titers were compared between mono- and co-inoculated dams in each compartment. Relative risks were calculated for outcomes that occurred in both groups. Tissue samples were also examined for evidence of pathophysiology.
RESULTS: Inoculation of pregnant mice with 107 GBS alone did not result in vaginal colonization or ascending infection. In contrast, co-inoculation of GBS with G. vaginalis in pregnant mice resulted in a 10-fold higher risk of GBS vaginal colonization (RR:10.31, 95%CI: 2.710-59.04; P=0.0006, Fishers Exact). Ascending GBS infection of the uterus and placenta occurred in approximately 40% of co-inoculated animals, whereas none of those receiving GBS alone developed uterine or placental infections. Immunofluorescence microscopy revealed GBS in both the maternal and fetal side of the placenta. Histological inflammation and increased pro-inflammatory cytokines were evident in the setting of GBS placental infection. Interestingly, placentas from dams exposed to GBS and G. vaginalis, but without recoverable vaginal or placental bacteria, displayed distinct histopathologic features and cytokine signatures.
CONCLUSION: These data suggest that G. vaginalis vaginal exposure can promote GBS vaginal colonization, resulting in greater likelihood of invasive perinatal GBS infections. These findings suggest that future clinical studies should examine whether the presence of G. vaginalis is a risk factor for GBS vaginal colonization in women. Since G. vaginalis can also be present in women without BV, these findings may be relevant both inside and outside of the context of vaginal dysbiosis.