The Female Reproductive Microbiome: Mechanistic Insights and Bioengineering Perspectives

Microbiota has emerged as a potential regulator of female reproductive health through immunological, metabolic, and endocrine networks. Growing evidence suggests that the composition and stability of the vaginal, uterine, and gut microbiota are associated with fertility outcomes. Disruptions in reproductive tract homeostasis have been linked to infertility, implantation failure, pregnancy loss, and diminished success in assisted reproductive technologies. Beyond local interactions, maternal gut microbiota may influence systemic immunity and metabolic pathways related to vaginal and endometrial microbiota. While these findings highlight the microbiome-based signatures' potential as predictive and prognostic biomarkers, their clinical applicability remains unconfirmed. Evidence is limited by small cohort sizes, methodological and analytical heterogeneity, and lack of standardization, limiting clinical translation. This narrative review summarizes the current knowledge regarding the microbiome's role in female reproductive health, highlighting its potential impact on pathophysiology, diagnostics, and therapeutic strategies. While this approach allows for a broad conceptual overview, we explicitly note that it is not systematic. As a result, this review is limited by the absence of a standardized search protocol, which may introduce selection bias. Finally, we review advances in microbial engineering and synthetic biology, highlighting engineered living biotherapeutics as promising strategies to improve microbiome-based reproductive medicine.