Unraveling Stage-Specific Metabolites in Human Milk and Their Links to Maternal Physiology: Insights from a Mexican Population

Background/Objective: Human milk is an irreplaceable source of nutrition, is essential for the infant’s growth and development right after birth and for early life stages survival. This study aims to characterize and compare the metabolite profiles of colostrum, transitional, and mature milk using an untargeted GC-MS approach. Additionally, it explores potential correlations between the identified metabolites and maternal nutritional factors. Methods: This was a longitudinal, prospective, and observational study. We included human milk samples from 113 Mexican women who practiced exclusive breastfeeding. Partial least squares-discriminant analysis (PLS-DA) was performed to assess differences among milk types. Metabolites showing significant variation across lactation stages were further analyzed using Friedman tests with post hoc Wilcoxon tests and Bonferroni correction. Correlations with maternal anthropometric were evaluated. Results: Twenty-three metabolites were identified, including amino acids and derivatives, sugars, fatty acids, and energetic metabolites. Alanine and creatinine decreased during lactation, while aspartate, serine, and valine increased. Rhamnose was higher in colostrum, whereas decanoic, dodecanoic, and tetradecanoic acids increased over time, and 11,14-eicosadienoic acid decreased. Lactic acid declined across stages. Positive correlations were found between several amino acids and maternal anthropometric variables, while lactic acid correlated negatively. Conclusions: Human milk metabolomic profiles display distinct, stage-specific variations shaped by maternal characteristics, reflecting the dynamic physiological and nutritional demands of the developing infant.