The vaginal microbiota has demonstrated associations with women's and newborns' health. Despite its comparatively simple composition relative to other human microbiota systems, the ecological processes that underpin the dynamics and stability of vaginal microbial communities remain mechanistically elusive. A crucial, yet so far underexplored, aspect of vaginal microbiota ecology is the role played by nutritional resources. Glycogen and its derivatives, produced by vaginal epithelia, are accessible to all bacterial constituents of the microbiota. Concurrently, free sialic acid and fucose offer supplementary nutritional resources for bacterial strains capable of cleaving them from glycans, which are structurally integral to mucus. Notably, bacteria adept at sialic acid exploitation are often correlated with adverse clinical outcomes and are frequently implicated in bacterial vaginosis (BV). In this study, we introduce a novel mathematical model tailored to human vaginal microbiota dynamics to explore the interactions between bacteria and their respective nutritional landscapes. Our resource-based model examines the impact of the relative availability of glycogen derivatives (accessible to all bacterial species) and sialic acid (exclusive to some BV-associated bacteria) on the composition of the vaginal microbiota. Our findings elucidate that the prevalence of BV-associated bacteria is intricately linked to their exclusive access to specific nutritional resources. This private access fortifies communities dominated by BV-associated bacteria, rendering them resilient to compositional transitions. We provide empirical support for our model's predictions from longitudinal microbiota composition and unpublished metabolomic data, collected from a North American cohort. The insights gleaned from this study shed light on potential pathways for BV prevention.
Significance statement: The vaginal microbiota has a notable impact on women's health at various stages of life, namely puberty, infection protection, sexual health, fertility, pregnancy, and menopausal changes. Yet, even though women frequently seek out treatment of vaginal symptoms, most non-anti-microbial products emphasise competitive interactions through acids (boric or lactic acid) or probiotics as a means to "rebalance" microbiota communities. However, despite recent advances in profiling the composition of vaginal microbiota communities, there remains a major gap in our mechanistic understanding of how to maintain or reinstate a resilient Lactobacillus -dominated microbiota that improves vaginal health and outcomes. This study explores the role of nutritional resources in the vaginal microbiota by introducing a mathematical model that analyses how access to specific nutrients like glycogen derivatives and sialic acid affects the balance of bacterial vaginosis (BV) and non-BV-associated bacteria. Results, supported by original cohort-derived microbiological and metabolomics data, show that exclusive access to these nutrients is linked to the dominance and resilience of BV-associated bacteria, providing new insights for BV prevention and treatment.