Abstract
Author(s): Jaworowicz Anna, Piasecka Joanna, Golembiewski Bartosz, Mulski Grzegorz, Manicka Martyna, Baranowicz Michal, Mazurkiewicz Weronika, Borecka Zuzanna, Sobczak Agnieszka Marta, and Szymczak Alicja
Background: Recurrent Pregnancy Loss (RPL) is a multifactorial condition in which more than half of cases remain unexplained despite advances in genetic, anatomical, endocrine and immunological evaluation. Growing evidence indicates that host-associated microbial ecosystems across the female and male reproductive tracts, as well as the gastrointestinal tract, exert significant influence on implantation, early placentation and maternal-fetal immune tolerance. This narrative review synthesizes current data on the vaginal, cervical, endometrial, gut and seminal microbiota in the context of RPL. Across the lower and upper reproductive tract, a Lactobacillus-dominant profile is consistently associated with reduced mucosal inflammation, preserved epithelial barrier integrity and a cytokine environment conducive to early gestational tolerance. Dysbiosis (characterized by Lactobacillus depletion, enrichment of anaerobes, increased microbial diversity or expansion of taxa linked to bacterial vaginosis) is repeatedly associated with heightened local inflammation, impaired endometrial receptivity, altered immune cell recruitment and suboptimal embryoendometrium interactions. Endometrial dysbiosis additionally correlates with chronic endometritis and perturbed maternal-fetal immune adaptation. Gut microbiome alterations, particularly loss of short-chain fatty acid-producing taxa and metabolite disturbances influencing systemic immune tone, appear to promote pro-inflammatory cytokine profiles implicated in RPL pathogenesis. The seminal microbiome may also contribute through microbe-driven oxidative stress, increased sperm DNA fragmentation, altered seminal cytokine milieu and semenmediated modulation of the female immune response at conception. Although causal relationships remain incompletely defined, evidence supports a model in which multisite microbial-immune interactions influence early pregnancy stability. The heterogeneity and methodological limitations of available studies highlight the need for standardized multisite profiling, longitudinal designs and mechanistic trials evaluating targeted microbiome-directed interventions. Understanding these microbial contributions may open future translational avenues for personalized diagnostic and therapeutic strategies in RPL