Supraphysiological Estradiol During Ovarian Stimulation Reveals Microbiome Resilience and Prevotella Opportunism

How the oral ecosystem responds to acute, high-amplitude hormonal perturbations remains poorly defined. Here we exploit controlled ovarian hyperstimulation (COH), a pharmacologically defined model that elevates systemic estradiol (E2) [~]100-fold above physiological baseline to dissect the multi-layer response of the oral environment in ten healthy oocyte donors. Integrating paired serum and salivary hormone quantification with subgingival metatranscriptomics, we identify a dual principle governing the oral ecosystem under acute endocrine stress. First, salivary E2 reliably tracks intra-individual systemic dynamics, confirmed by robust linear regression, establishing saliva as a non-invasive endocrine proxy even under supraphysiological conditions. Second, despite the dramatic hormonal surge, the subgingival metatranscriptome exhibited functional resilience with no differentially expressed genes detected across two independent bioinformatic pipelines while a core of 20,687 genes remained stably expressed at both timepoints, underscoring the robustness of established biofilm communities. This global stability was selectively broken by four Prevotella species, whose abundance increased proportionally to salivary E2 elevation, consistent with their steroid hormone auxotrophy. Together, these findings reveal that the subgingival microbiome is functionally buffered against acute hormonal perturbation yet harbors estrogen-sensitive taxa capable of exploiting endocrine surges as ecological opportunities, with potential implications for reproductive and systemic inflammatory health.