Maternal Microbiome in Fetal Programming: A One Health Perspective on Translational Implications for Early-Life Health

Pregnancy represents a critical eco-biological window during which maternal physiology integrates environmental exposures, lifestyle factors, and interconnected microbial ecosystems to shape fetal development and long-term health. From a One Health perspective, defined here as the interconnection between maternal health, environmental determinants, and microbial ecosystems across generations, the maternal microbiome functions as a dynamic interface linking the external environment to the intrauterine milieu, translating ecological signals into immunological, metabolic, and neuroendocrine pathways that influence placental function and developmental programming. Across gut, vaginal, oral, and mammary niches, maternal microbial communities operate as an integrated network regulating systemic inflammation, metabolic homeostasis, and the production of bioactive metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives. This review proposes an integrated systems framework in which pregnancy is viewed as a transient ecological system shaped by ten interconnected maternal determinants, encompassing microbial niches, nutrition, lifestyle factors, medical interventions, mode of delivery, and postnatal microbial transmission, that converge on shared microbiome-mediated signaling pathways affecting fetal and neonatal immune, metabolic, and neurodevelopmental trajectories. Broader macro-environmental drivers, including biodiversity loss, urbanization, pollution, and industrialized lifestyles, are considered as upstream modulators of maternal microbial ecology within a One Health context. A systems model is presented to illustrate how environmental inputs are biologically transduced through maternal microbial networks to influence placental function, fetal development, and early-life health trajectories. Framing pregnancy as an integrated eco-biological continuum highlights the maternal microbiome as a central hub of intergenerational health and may support microbiome-informed preventive strategies and public health approaches aimed at reducing the burden of non-communicable diseases (NCDs) of early-life origin.