Gut microbiome and metabolite profiling in term SGA infants: a multi-omics approach to physical development

Early-life gut microbial composition and fecal metabolic profiles may be altered in infants born small for gestational age (SGA), but evidence specifically concerning term SGA infants remains limited. To characterize gut microbial composition, predicted microbial functions, and fecal metabolite profiles in term SGA infants and explore their associations with early growth. This prospective nested case–control study included 62 term infants (31 SGA and 31 appropriate for gestational age [AGA]). Fecal samples were collected at 3 months. Untargeted metabolomics was performed in the full cohort, and shotgun metagenomic sequencing was conducted in a nested subset of 20 infants (10 SGA and 10 AGA). Differential taxa, KEGG orthologs (KOs), metabolites, and cross-omics correlations were analyzed. Alpha diversity did not differ significantly between groups, whereas microbial composition and species-level abundance patterns differed between SGA and AGA infants. Functional analysis identified 135 differential KOs, including 36 with higher and 99 with lower abundance in the SGA group. These KOs were mapped to 25 metabolic pathways, including galactose, butanoate, D-amino acid, aromatic amino acid, fructose–mannose, pyruvate, propanoate, and lipid metabolism. Twelve fecal metabolite features differed between groups, including 5′-methylthioadenosine, taurocholate, β-alanine, and 17α-hydroxypregnanolone. Exploratory integration identified connections among microbial species, KOs, and metabolites. Several microbial and metabolite features showed nominal associations with 6-month growth indices, but most cross-omics and metabolite–growth associations did not remain significant after false discovery rate correction. Term SGA infants showed differences in gut microbial composition, predicted metabolic potential, and fecal metabolite profiles at 3 months. Associations with subsequent growth were exploratory and require validation in larger longitudinal studies.