1H NMR-Based Metabolomic Profiling and Comparison of Human Milk across Different Lactation Stages in Secretors and Nonsecretors: A Study of Chinese Lactating Women.

Background: Human milk oligosaccharides (HMOs) and other milk-derived metabolites are crucial for infant health, influencing gut microbiota and overall development.

Objective: This study aimed to uncover insights into the variations of HMOs and non-HMO metabolites based on secretor (Se) status, lactation time, mode of delivery, and infant sex.

Methods: An exploratory cross-sectional study was designed to compare the concentrations of HMOs and non-HMOs metabolites in milk samples from 129 lactating Chinese women within 1 y postpartum. Nuclear magnetic resonance analysis was employed for the identification and quantification of the metabolites. The metabolites measured were grouped into sugars, free amino acids, fatty acids, and metabolites related to energy metabolism. The influences of delivery mode and infant sex on milk metabolite composition were explored.

Results: Uniform Manifold Approximation and Projection analysis of HMOs profiles revealed distinct clustering based on Se status, with significant differences in 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) concentrations observed between Se+ and Se- groups. A decreasing trend for 2'-FL and 6'-sialyllactose concentrations, along with an increase in 3-FL concentrations, was observed with increasing lactating period within 12 mo postpartum. Non-HMOs metabolite analysis indicated that Se status only affected glutamate concentrations. An increase in glutamine concentrations was observed 3-9 mo postpartum. A continuous increase in o-phosphocholine concentrations was noted in 12 mo postpartum, along with reductions in citrate and sn-glycero-phosphocholine concentrations. Delivery mode and infant sex did not affect both HMOs and non-HMOs concentrations.

Conclusions: Metabolomic analysis of human milk reveals significant variation of HMOs, but not in non-HMOs, based on Se status. Changes in certain HMOs and non-HMOs concentrations were also observed over the 1 y of lactation. Understanding how these metabolites change over time may influence recommendations for maternal diet, supplementation, and the timing of breastfeeding to ensure optimal nutrient delivery to the infant.