From maternal microbial transmission to neonatal gut microbiota restoration: the potential and challenges of maternal fecal microbiota transplantation

Early-life gut microbiota establishment is a critical developmental process shaped by maternal microbial transmission and ecological succession. Microorganisms from the maternal gut, vagina, breast milk, skin, and oral cavity contribute to neonatal microbial acquisition, while strain-resolved studies increasingly support the maternal gut as an important reservoir of strains capable of persistent colonization in the infant intestine. This transmission can be disrupted by cesarean delivery, prematurity, perinatal antibiotic exposure, and neonatal intensive care, resulting in delayed acquisition of maternal commensals, altered microbial succession, and increased colonization by opportunistic microorganisms. Current restoration strategies, including probiotics, synbiotics, and vaginal microbiota seeding, can modify early microbial communities but do not fully reproduce the diversity, maternal specificity, and persistence of naturally transmitted maternal gut strains. Maternal fecal microbiota transplantation (FMT) has therefore emerged as a potential strategy to restore disrupted maternal gut-to-infant microbial transmission. Initial proof-of-concept and strain-resolved studies suggest that carefully screened maternal FMT can increase mother-to-infant strain sharing, promote recovery from cesarean-associated microbiota perturbations, and reduce colonization by potential pathogens. However, evidence for durable engraftment, functional benefits, clinical efficacy, and long-term safety remains limited. Future studies should prioritize rigorous donor screening, standardized intervention protocols, appropriate recipient selection, and longitudinal integration of strain-resolved metagenomics, metabolomics, immune profiling, and clinical outcomes. Maternal FMT remains investigational but provides a promising framework for precision early-life microbiota restoration.