Title: 477: Microbial strain ecology of the vaginal microbiome in pregnancy and at postpartum
Abstract: It is postulated that the vaginal microbiome lends to the risk/prediction of preterm birth (PTB), although data demonstrating this is inconsistent. As microbiome function results from production of strain-specific metabolites, it is important to adequately characterize vaginal ecology at the strain level. Reliable strain detection requires deep metagenomic sequencing, which cannot be achieved with 16S approaches. Here we tested the hypothesis that keystone vaginal bacterial species are present as dissimilar strains that might differentially associate with PTB. In this prospective study we performed metagenomic sequencing (Illumina HiSeq) on microbial DNA extracted from vaginal samples (n=201, 60 gravidae) collected during 3rd trimester, delivery, and 4-6 weeks postpartum. Strain-level classification of bacteria was performed using PanPhlAn. Lactobacillus spp. are present as one of two strains, whereas Gardnerella vaginalis comprises five strains ( Fig1A). When we then examined interactions at the strain level, we found strain modeling mirrored species level co- occurrence models. However, we found L. crispatus and L. jensenii strains negatively co-occurred with Gardnerella strains; at the species level L. iners negatively and positively co-occurred with Gv2b and Gv3 strains, respectively (Fig1B). As exclusionary interactions between these taxa are thought to lead to PTB, we tested whether differences in strain frequencies associated with PTB. There was no significant difference in the frequency of multiple Gardnerella strains during pregnancy on PTB. When we examined the frequency of Gardnerella and lactobacilli strains, we also failed to identify clear associations with PTB (p>0.05) (Fig1C). Metagenomic sequencing, although costlier and more computationally intensive compared to 16S metabarcoding, provides a highly sensitive method for detecting the dominant members of the vaginal microbiome, enabling strain-level differentiation. The current findings are noteworthy, as they demonstrate for the first time the degree to which strain-level differences among dominant vaginal microbial species occur. The failure to see an association with PTB and strains likely explains the evident disparity among others PTB studies. Given these strain-level differences, we speculate larger studies will be required to definitively determine whether an association between the vaginal microbiome and PTB exists.