Escorcia Mora Patricia, Valbuena Diana, Diez-Juan Antonio
R&D Department, Igenomix (Part of Vitrolife Group), Ronda de Narcís Monturiol, nº11, B, Edificios Europark, Parque Tecnológico, 46980 Paterna, Valencia, Spain.
Life (Basel). 2025 May 9;15(5):762. doi: 10.3390/life15050762.
Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut-endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites-including short-chain fatty acids, bile acids, and tryptophan catabolites-in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host-microbiota interactions in female fertility.
生育能力是一个动态的、多因素的过程，受激素、免疫、代谢和环境因素的调控。最近的证据表明，肠道微生物群是生殖健康的关键全身调节因子，对子宫内膜功能、着床、妊娠维持和分娩时间有显著影响。本综述探讨了肠道-子宫内膜轴，重点关注肠道微生物群落如何通过分子信号通路影响生殖生物学。我们讨论了微生物衍生代谢产物（包括短链脂肪酸、胆汁酸和色氨酸分解代谢产物）在塑造子宫界面的免疫耐受、雌激素代谢和上皮完整性方面的调节作用。重点关注了诸如β-葡萄糖醛酸酶介导的雌激素循环、Toll样受体（TLR）驱动的炎症、Th17/Treg细胞失衡和微生物易位等共同机制，这些机制共同表明生态失调与包括子宫内膜异位症、多囊卵巢综合征（PCOS）、反复着床失败（RIF）、子痫前期（PE）和早产（PTB）在内的妇科疾病的病因有关。尽管目前的大多数证据仍然是相关性的，但宏基因组学和代谢组学分析以及微生物群耗竭模型和孟德尔随机化研究的新见解强调了肠道-生殖相互作用的生物学意义。通过整合微生物学、免疫学和生殖分子生物学的概念，本综述提供了一个关于宿主-微生物群在女性生育能力中相互作用的系统层面观点。
