Distinct Early-Life Gut Microbiota Patterns Across SGA, AGA, and LGA Infants

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Abstract

Purpose: 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. Methods: We prospectively enrolled 42 late preterm and term infants and classified them into SGA (n=12), AGA (n=20), and LGA (n=10). Serial fecal samples were collected at four postnatal time windows (0–7, 8–14, 15–28, and 29–80 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 MetaCyc and KEGG databases. Clinical variables including feeding pattern and antibiotic exposure were assessed. Results: Relative abundances did not differ significantly at the phylum or genus levels. However, Streptococcus salivarius and Streptococcus spp. abundance significantly increased in late LGA infants. Alpha diversity was significantly higher in the late SGA infants than the early LGA infants. Beta diversity analysis revealed significant microbial separation, with the late SGA infants forming a distinct microbial community from early AGA, early SGA, and late LGA infants. Co-occurrence network analysis revealed a stable gut microbiota in LGA infants. Conclusion: These findings highlight birth weight–dependent divergence in early gut microbiome development, suggesting that initial growth status shapes microbial maturation patterns and may influence subsequent health trajectories.

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