Microbes, molecules, and the maternal–fetal interface: rethinking the gut–placenta axis

Placental biology is increasingly framed through a signaling paradigm in which maternal microbiome-derived mediators-rather than microbial colonization-affect the function of the interface. This review synthesizes evidence that circulating microbial signals, including short-chain fatty acids, tryptophan-derived indoles, bile-acid-linked ligands, microbe-associated molecular patterns, and bacterial extracellular vesicles, are associated with placental vascular development, immune regulation, nutrient transport, and endocrine programs-processes central to pregnancy outcomes. We integrate mechanistic insights from gnotobiotic and supplementation models with limitations of human evidence and identify key translational gaps. The current evidence supports a model in which maternal microbial ecology shapes a network of circulating mediators that converge on interlinked placental pathways essential for placental function and fetal development.