ABSTRACT Breast milk can improve infant health by exerting beneficial effects on the developing gut microbiota and metabolites. However, infant formula composition undergoes continual refinement to better approximate breast milk. This study aimed to timely monitor the evolving disparities in the gut microenvironment between breastfed (BF) and formula‐fed (FF) infants. This prospective cohort study enrolled 44 healthy infants at 6 months of age, stratified by infant feeding modality into BF ( n = 27) and FF ( n = 17) groups. Fecal samples of all infants were collected and tested. Fecal microbiota was tested via full‐length 16S rRNA sequencing, and fecal metabolites were tested via untargeted UPLC‐MS/MS metabolomics. Associations between gut microbiota and metabolites were evaluated using Spearman's rank correlation test. Bacterial full‐length 16S rRNA gene sequencing analysis revealed that Escherichia, Staphylococcus, Haemophilus, and Rothia were more enriched in the BF group, but Enterococcus and Mediterraneibacter were more enriched in the FF group conversely ( p < 0.05). UPLC‐MS/MS metabolomic profiling revealed 600 dysregulated metabolites ( p < 0.05) discriminating BF and FF infants, with 225 metabolites up‐regulated and 375 metabolites down‐regulated in the BF group. Further analysis of the significantly differential metabolites of the top 100 Variable Importance in Projection (VIP) revealed that 12 metabolites could be mapped onto Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathways, in which the metabolites were mostly mapped onto Arachidonic acid (AA) metabolism and were down‐regulated in the BF group, including Thromboxane B2 (TXB2), 5‐hydroxyeicosatetraenoid acid (HETE), (15S)‐Prostaglandin A2 (PGA2), and 11‐dehydro‐TXB2. Breastfeeding establishes a distinct ecological imprinting on the infant gut, promoting specific taxa and downregulating pro‐inflammatory fecal AA metabolites. These disparities suggest breastfeeding uniquely modulates the microbial‐metabolic axis to maintain a lower inflammatory tone, offering immunological advantages despite modern formula innovations.
Zhu et al. (Wed,) studied this question.