A manifold-based framework for studying the dynamics of the vaginal microbiome.

The vaginal microbiome plays a crucial role in our health. The composition of this community can be classified into five community state types (CSTs), four of which are primarily consisted of Lactobacillus species and considered healthy, while the fifth features non-Lactobacillus populations and signifies a disease state termed Bacterial vaginosis (BV), which is associated with various symptoms and increased susceptibility to diseases. Importantly, however, the exact mechanisms and dynamics underlying BV development are not yet fully understood, including specifically possible routes from a healthy to a BV state. To address this gap, this study set out to characterize the progression from healthy- to BV-associated compositions by analyzing 8026 vaginal samples and using a manifold-detection framework. This approach, inspired by single-cell analysis, aims to identify low-dimensional trajectories in the high-dimensional composition space. It further orders samples along these trajectories and assigns a score (pseudo-time) to each analyzed or new sample based on its proximity to the BV state. Our results reveal distinct routes of progression between healthy and BV states for each CST, with pseudo-time scores correlating with community diversity and quantifying the health state of each sample. Several BV indicators can also be successfully predicted based on pseudo-time scores, and key taxa involved in BV development can be identified using this approach. Taken together, these findings demonstrate how manifold detection can be used to successfully characterize the progression from healthy Lactobacillus-dominant populations to BV and to accurately quantify the health condition of new samples along the route of BV development.