(258) Common vaginal microbes modify energy metabolism and oxidative balance: potential implications on reproductive health

Host-microbial interactions in the cervicovaginal space modify reproductive outcomes. While Lactobacillus crispatus (LC) supports vaginal health, anaerobes like Gardnerella vaginalis (GV) have been implicated in pathologic processes, such as preterm birth. Our study leveraged global metabolomics as a biochemical window into these complexities.


Study Design:

We used an in vitro host cell-microbial co-culture model. Vaginal, ectocervical, and endocervical epithelial cells, and THP-1-derived macrophages (MØs) were treated with 10⁵-10⁷ CFUs of LC or GV for 24h. We conducted untargeted metabolomics on cell culture media (n=3/condition). Log₂ transformed batch-normalized data were analyzed by two-way ANOVA (p < 0.05) with calculation of false discovery rates (q < 0.1). Primary component analysis was performed with total variance as a sum of variances of predicted values of each component.


Results:

Experimental groups clustered by treatment for epithelial cells, while MØs grouped separately (Fig. 1). Compared to non-treated control, both LC and GV increased numerous metabolites across pathways; fewer metabolites were decreased by microbial exposure (data not shown). While both LC and GV increased branched chain amino acid metabolites, GV exerted a more robust effect, suggesting increased GV-utilization of nitrogen energy sources. LC increased lactate derivatives, reflecting rapid glucose utilization. GV increased polyamine, phospholipid, and oxidative stress metabolites, potentially signifying cell membrane breakdown or turnover. Top differentially detected metabolites, all increased by microbial exposure, are presented in Table 1.


Conclusion:

Our data reveal differences in energy metabolism and oxidative balance in response to common vaginal microbes. As metabolites may serve as chemical messengers, our findings provide a biochemical lens through which the complexities of host-microbial communication may be more clearly discerned. Modification of this metabolic milieu carries translational potential to mitigate risk of adverse reproductive outcomes. University of Pennsylvania Research Foundation Award (KG)