The maternal and infant gut microbiome: implications for pregnancy outcomes, immune development, and health in the first 1000 days

The maternal microbiota is recognized as an important regulator of pregnancy outcomes and early infant immune programming. Across gestation, microbial communities in the gut, vaginal, oral, and putative placental niches undergo dynamic changes driven by hormonal, metabolic, and environmental factors, with important consequences for maternal–fetal health. These microbial transitions shape maternal immune-metabolic balance and are associated with major pregnancy complications, including gestational diabetes mellitus, preeclampsia, intrahepatic cholestasis of pregnancy, fetal growth restriction, and preterm birth. Emerging yet debated evidence suggests that microbial DNA signatures may be detected in the placenta and uterus, raising critical questions about in utero microbial transmission and its role in neonatal microbiota establishment. The first 1,000 days, spanning prenatal life through early childhood, represent a critical window during which the infant gut microbiota is established and immune programming begins. Maternal–infant microbial transfer occurs through delivery, breastfeeding, and early-life environmental exposures, seeding the neonatal gut with beneficial taxa such as Bifidobacterium and shaping immune tolerance through mediators including IgA, TGF-β, and human milk oligosaccharides. Perturbations during this period via cesarean delivery, antibiotic exposure, or maternal dysbiosis have been associated with higher risks of allergy, autoimmunity, obesity, and neurodevelopmental abnormalities later in life. This review synthesizes current findings on maternal–infant microbiome interactions, emphasizing their role in immune maturation and disease susceptibility. It also discusses emerging therapeutic strategies—including probiotics and prebiotics, fecal microbiota transplantation, next-generation microbial ecosystem therapeutics, and CRISPR-based approaches that are under investigation for modulating the maternal and infant microbiome. Despite significant advances, key gaps remain in establishing the existence of a true placental microbiome, the mechanisms of maternal immune–microbial signaling, and the long-term efficacy of microbiome-targeted therapies. Understanding the intricate crosstalk between microbiota, hormones, and immunity provides a foundation for developing approaches to improve maternal and child health.