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.激素波动是女性生理机能的核心调控因素，但其对黏膜生态系统的急性影响仍有待深入阐明。本研究以控制性卵巢过度刺激（controlled ovarian hyperstimulation, COH）作为模拟超生理水平雌二醇（estradiol, E2）波动的独特人体体内模型，对口腔生态系统展开探究。我们招募了10名因卵子捐赠接受COH治疗的健康女性，分别在刺激治疗前及全身雌二醇浓度达峰值时，采集其配对的唾液与龈下菌斑样本。唾液中的雌二醇浓度与全身激素波动高度吻合，证实即便在极端激素水平范围内，唾液仍可作为反映内分泌状态的动态无创替代标志物。相较之下，尽管全身内分泌状态发生扰动，龈下宏转录组仍表现出显著的功能稳定性，未检测到全球微生物基因表达的显著变化。这一表观稳定性背后实则存在类群特异性应答：普氏菌属（Prevotella）物种的相对丰度随唾液雌二醇水平升高而显著增加，这与其已知的激素依赖性代谢能力相符。综上，本研究揭示了口腔生态系统的双重特性：全球微生物功能对急性内分泌扰动具有耐受性，而雌激素敏感性类群则可利用激素波动作为生态位拓展的契机。本研究证实COH是探究激素-微生物组互作的可操作性人体模型，同时确立了口腔作为激素响应性储库的地位，其研究结果对全身性炎症与生殖健康具有参考价值。