Distinct early-life gut microbiota patterns across SGA, AGA, and LGA infants

Birthweight-for-gestational-age influences neonatal physiology and health, yet its role in shaping early gut microbiome development remains insufficiently defined. Small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), and large-for-gestational-age (LGA) infants may exhibit distinct microbial maturation patterns that could influence later metabolic and developmental outcomes. We conducted a prospective cohort study and enrolled 50 late-preterm and term infants and classified them into SGA (n=18), AGA (n=20), and LGA (n=12). Serial fecal samples were collected at four postnatal time windows (0-14 and 15-80 days). 16S rRNA gene sequencing using Oxford Nanopore MinION characterized microbial composition, diversity, and community networks. Bioinformatic analyses included alpha- and beta-diversity metrics, co-occurrence network analysis, and functional pathway inference using PICRUSt2 mapped to the MetaCyc database. Clinical variables, including feeding pattern and antibiotic exposure, were assessed. Gut microbiome development differed according to birthweight categories. Microbial diversity increased with postnatal age, with SGA infants showing distinct community structures over time. Firmicutes predominated across all groups, while specific taxa exhibited group-specific patterns, including enrichment of Streptococcus spp. in LGA infants and Klebsiella spp. in SGA infants. Co-occurrence network analysis revealed a stable gut microbiota in LGA infants.

Birthweight-for-gestational-age status was associated with distinct trajectories of early gut microbial maturation. SGA infants exhibited delayed microbial stabilization and fragmented interaction networks, whereas LGA infants demonstrated relatively early establishment of stable, Streptococcus-enriched communities. These growth-specific microbial patterns may reflect differences in early metabolic programming and highlight the potential importance of tailored microbiome-targeted strategies to optimize neonatal development.

• Abnormal fetal growth is associated with increased neonatal morbidity and long-term metabolic risk. • Early-life gut microbiota play an important role in immune and metabolic development.

• This longitudinal study demonstrates growth-specific trajectories of early gut microbial maturation among SGA, AGA, and LGA infants born at ≥35-week gestation. • SGA infants exhibit delayed microbial stabilization and fragmented microbial interaction networks, whereas LGA infants show relatively earlier establishment of stable microbial communities.