Sub-communities of the vaginal microbiota in pregnant and non-pregnant women

Abstract Diverse and non- Lactobacillus -dominated vaginal microbial communities are associated with adverse health outcomes such as preterm birth and the acquisition of sexually transmitted infections. Despite the importance of recognizing and understanding the key risk-associated features of these communities, their heterogeneous structure and properties remain ill-defined. Clustering approaches are commonly used to characterize vaginal communities, but they lack sensitivity and robustness in resolving substructures and revealing transitions between potential sub-communities. Here, we address this need with an approach based on mixed membership topic models, using longitudinal data from cohorts of pregnant and non-pregnant study participants. We identify several non- Lactobacillus -dominated sub-communities common to both cohorts and independent of reproductive status. In non-pregnant individuals, we find that the menstrual cycle modulates transitions between and within sub-communities. In addition, a specific non- Lactobacillus -dominated sub-community, which was associated with preterm delivery in pregnant participants, was also more common during menses, a time of elevated vaginal inflammation in non-pregnant participants. Overall, our analyses based on mixed membership models reveal substructures of vaginal ecosystems which may have important clinical and biological associations.