Abstract
BACKGROUND: The neonatal period is critical for oral microbiome establishment, but temporal patterns in preterm newborns remain unclear. This study examined longitudinal microbiome changes in full-term and preterm newborns and assessed perinatal and clinical influences. METHODS: Oral swabs were collected from 98 newborns (23 full-term, 75 preterm). Samples were obtained at birth and Day 2 for full-term, and at birth, Day 7, and Day 28 for preterm newborns. 16S rRNA gene sequencing was used to analyze microbial diversity, taxonomic shifts, and virulence-related genes. RESULTS: Preterm newborns showed persistently lower α-diversity and delayed succession compared with full-term newborns. Full-term infants transitioned rapidly from Proteobacteria-dominant to Firmicutes- and Actinobacteria-rich communities, while preterm infants maintained Proteobacteria longer. Diversity in preterm newborns was significantly affected by gestational age, birthweight, delivery mode, feeding type, and β-lactam exposure. Breastfeeding supported more stable diversity, whereas cesarean delivery and formula feeding reduced diversity. Functional profiling revealed greater abundance of virulence-associated genes in preterm newborns, suggesting differences in early host-microbe interactions. . CONCLUSIONS: Preterm newborns exhibit delayed oral microbiome development, influenced by multiple modifiable factors. Supportive strategies, such as breastfeeding and prudent antibiotic use, may help foster microbial stability and potentially reduce infection risk in this vulnerable population.