Ruxue Zhou, Shenglan Wang
Pregnancy is a unique physiological stage characterized by the coordinated remodeling of maternal metabolism, immunity, and endocrine systems. Previous studies have primarily focused on the local uterine microenvironment, neglecting the role of the maternal gut microbiota in mediating distal, cross-organ regulation via the gut-placental axis. The concept of the gut-placental axis was formally proposed in 2018 and has attracted widespread research attention in recent years. Studies using germ-free animals, fecal microbiota transplantation (FMT), and in vitro experiments with human multi-omics cohorts suggest that live gut bacteria generally cannot colonize the placenta, and that soluble microbial metabolites mediate bidirectional signaling between the gut and the placenta. Pregnancy-related factors such as a high-sugar, high-fat diet, antibiotic use, and obesity can induce gut microbiota dysbiosis and intestinal barrier dysfunction, leading to decreased levels of potentially protective metabolites such as short-chain fatty acids (SCFAs) and tryptophan derivatives, while pro-inflammatory molecules such as lipopolysaccharide (LPS), and trimethylamine N-oxide (TMAO) to accumulate in the bloodstream. These substances cross the placental barrier, disrupting maternal-fetal immune homeostasis, inhibiting trophoblast function and spiral artery remodeling, and are statistically associated with adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and spontaneous preterm birth. This article is a narrative review that systematically elucidates the - placental axis for substance transport and the potential molecular mechanisms by which metabolites regulate maternal-fetal immune balance; it maps out the pathological pathways through which microbiota dysbiosis mediates various adverse pregnancy outcomes; it objectively analyzes controversies and gaps in areas such as placental microbial colonization, bidirectional feedback loops, and evidence for clinical interventions; and it proposes a future research framework centered on multi-omics candidate biomarkers and stratified microbiome interventions. Microbial metabolites are promising candidates for non-invasive biomarkers; stratified microbiome interventions are merely potential prevention and control strategies suggested by laboratory and small-scale clinical studies. There is still a lack of unified, standardized clinical protocols, and large-scale, long-term, randomized controlled trials (RCTs) are needed to validate their safety and efficacy, thereby providing a theoretical foundation for subsequent mechanistic and translational research on maternal-fetal microbiome interactions.