Underexplored maternal microbiomes: immune, metabolic, and microbial pathways shaping pregnancy outcomes

Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial signaling, the role of environmental and social determinants in shaping these ecosystems, and mechanisms by which microbes or their products influence host physiology without direct colonization. We also consider the translational potential of microbiota-based interventions to safely improve pregnancy outcomes. Finally, we identify major knowledge gaps and research priorities necessary to advance a more integrated understanding of maternal microbial influences on reproductive and neonatal health. Our synthesis reframes the maternal microbiome as a coordinated, multi-site network that modulates systemic immune and metabolic pathways critical for reproductive success. Understanding these connections will open new avenues for predicting, preventing, and treating pregnancy-related disorders through precision microbiome science.