Neonatal Microbiome: Early Colonization, Preterm Dysbiosis, and Clinical Implications

The neonatal microbiome constitutes a dynamic and rapidly evolving ecosystem that exerts profound effects on immune, metabolic, and neurodevelopmental processes during early life. This review synthesizes current evidence on the establishment, maturation, and functional roles of the neonatal microbiome, emphasizing the differences between preterm and term infants and their implications for neonatal diseases. Microbial colonization commences at birth and is shaped predominantly by maternal transmission, mode of delivery, feeding practices, and antibiotic exposure. The early assembly of oral and gut microbiota provides the foundation for immune education, intestinal barrier integrity, and metabolic homeostasis; however, disruptions during this critical developmental window are associated with adverse outcomes. Preterm infants exhibit delayed and dysbiotic microbial development, characterized by reduced diversity, enrichment of Proteobacteria, and depletion of short-chain fatty acid-producing taxa. These alterations are strongly implicated in the pathogenesis of necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, and neurodevelopmental impairment, predominantly through mechanisms involving exaggerated lipopolysaccharide—Toll-like receptor 4—nuclear factor kappa B signaling, impaired barrier function, and metabolic deficiencies. Advances in germ-free and gnotobiotic models, combined with multi-omics approaches, have elucidated key host–microbe interactions and mechanistic pathways underpinning neonatal health. However, major challenges persist in establishing causality, standardizing analytical methods, and translating mechanistic findings into effective clinical interventions. Understanding the neonatal microbiome as a central regulator of early-life programming holds promise for the development of microbiome-targeted preventive and therapeutic strategies in neonatal and pediatric medicine.