Maternal obesity influences transcriptomic and metagenomic profiles in term neonates

Maternal obesity impacts neonatal outcomes; however, its influence on fetal gene expression and early gut microbiota composition remains insufficiently characterized. This prospective study was conducted in 62 full-term neonates between 2022 and 2024, analyzing transcriptomic profiles from umbilical-cord blood and metagenomic sequencing of fecal samples at 4 months. The cohort included 31 neonates born to mothers with normal BMI (NBMI) and 31 neonates born to mothers with overweight or obesity (OBMI). Major congenital anomalies, maternal exposure to drugs or antibiotics were exclusion criteria. OBMI neonates demonstrated significant upregulation of genes related to inflammation (MPO, OLR1) and cell-cycle dysregulation (GADD45G, CCNA1). Evidence of altered lysosomal function was observed, with increased expression of CTSG and CLTCL1 and reduced expression of HYAL1. Microbiome analysis revealed a decrease in Bacteroidota and an increase in Proteobacteria in cesarean-delivered neonates. Holdemanella was enriched in vaginally delivered OBMI neonates, suggesting a potential adaptive microbial response. Enrichment of opportunistic pathogens, including Klebsiella, Morganella, and Enterococcus, was observed in cesarean-delivered neonates, indicating a combined effect of maternal obesity and delivery mode on early microbial colonization. These findings suggest that maternal obesity modifies neonatal immune and metabolic gene expression while reshaping gut microbiome composition, with potential implications for long-term health.