Shotgun metagenomics of vaginal samples from pregnant women at risk of preterm birth

An association between the vaginal microbiota and preterm birth (PTB) has been reported in several research studies. Population shifts from high proportions of lactobacilli to mixed species communities, as seen with bacterial vaginosis, have been linked to a 2-fold increased risk of PTB. Despite the increasing number of studies using next generation sequencing technologies, primarily involving 16S rRNA-based approaches, to investigate the vaginal microbiota during pregnancy, no distinct microbial cause of PTB has been determined. Shotgun metagenomic sequencing offers a powerful tool to reveal community structures and their gene functions at a far greater resolution than amplicon sequencing. In this study, we employ shotgun metagenomic sequencing to compare the vaginal microbiota of women at high risk of preterm birth versus a low risk control group. While microbial diversity and richness did not differ between groups, there were significant differences in terms of individual species. In particular, Lactobacillus crispatus was strongly associated with samples from a full-term pregnancy, whilst the community state-types 4 and 5 were associated with samples from preterm pregnancies. Furthermore, the functional potential of the preterm microbiota was distinct from that of its full-term equivalent. Taken together, there is a discrete structural and functional difference in the microbial composition of the vagina in women who deliver preterm.