Antimicrobial Stewardship During Lactation: Current Evidence on the Human Milk–Infant Microbiome Axis and Neurodevelopment

Human milk is increasingly recognized as a complex biological system that contributes to infant development through nutritional, immunological, and microbial pathways. Simultaneously, antimicrobial stewardship (AMS) has become a global healthcare priority because of rising antimicrobial resistance and concerns regarding the ecological consequences of antibiotic exposure during early life. This narrative review examines current evidence regarding the impact of anti-infective therapies during lactation on the maternal–infant microbiome axis and discusses the role of AMS in supporting appropriate maternal treatment while preserving breastfeeding. While previous reviews have independently described the biological properties of human milk or general antimicrobial resistance, this narrative review uniquely bridges these domains by framing the infant microbiome as a clinical endpoint for pharmacological governance. The primary objective is to synthesize current evidence on the relationships among human milk, the infant gut microbiome, and neurodevelopment, with a novel emphasis on how integrating Antimicrobial Stewardship (AMS) and microbiome-conscious prescribing during lactation actively safeguards these developmental trajectories. This work contributes to the existing literature by shifting the focus from observational biology to an actionable clinical framework for healthcare providers. A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science. Studies addressing human milk biology, infant gut microbiota development, antimicrobial exposure during lactation, microbiota–gut–brain interactions, and stewardship strategies were reviewed. Available evidence indicates that breastfeeding promotes the establishment of a beneficial gut microbiota and supports immune maturation through the combined action of human milk oligosaccharides, immunological factors, and milk-associated microorganisms. Maternal and neonatal antibiotic exposure may alter microbial colonization patterns; however, the magnitude, persistence, and long-term clinical significance of these effects remain incompletely understood. Although mechanistic studies support biologically plausible links between microbiome alterations and neurodevelopmental pathways, direct evidence connecting maternal antibiotic use during lactation with adverse neurodevelopmental outcomes is limited. Current evidence supports continued breastfeeding during most maternal antibiotic treatments and highlights the importance of microbiome-conscious prescribing. AMS strategies based on diagnostic appropriateness, treatment optimization, and avoidance of unnecessary antibiotic exposure may help minimize microbial disruption while ensuring effective infection management.