Microbial Resilience and Functional Gene Adaptation to Acute Estradiol Surges

Hormonal surges are fundamental drivers of female physiology, yet their acute impact on mucosal ecosystems remains poorly understood. Here we used controlled ovarian hyperstimulation (COH) as a unique in vivo human model of supraphysiological estradiol (E2) fluctuations to probe the oral ecosystem. In ten healthy women undergoing COH for oocyte donation, paired saliva and subgingival plaque samples were collected before stimulation and at peak systemic E2. Salivary E2 concentrations mirrored systemic surges, confirming saliva as a dynamic, non-invasive proxy of endocrine status even under extreme hormonal ranges. By contrast, the subgingival metatranscriptome displayed remarkable functional resilience with no significant shifts in global microbial gene expression were detected despite systemic endocrine perturbation. This apparent stability was nuanced by a taxon-specific response, Prevotella species significantly increased in relative abundance in proportion to salivary E2 elevations, consistent with their known hormone-dependent metabolic capabilities. Together, these findings reveal a dual principle in the oral ecosystem as global microbial functions are resilient to acute endocrine perturbations, yet estrogen-sensitive taxa exploit hormonal surges as ecological opportunities. This study establishes COH as a tractable human model to investigate hormone–microbiome interactions, positioning the oral cavity as a hormone-responsive reservoir with implications for systemic inflammatory and reproductive health.