Human milk microbiota and oligosaccharides in colostrum and mature milk: comparison and correlation.

Background: The interaction between the human breast milk microbiota and human milk oligosaccharides (HMOs) plays a crucial role in the healthy growth and development of infants. We aimed to clarify the link between the breast milk microbiota and HMOs at two stages of lactation.

Methods: The microbiota and HMOs of 20 colostrum samples (C group, 1-5 days postpartum) and 20 mature milk samples (S group, 42 days postpartum) collected from postpartum mothers were analyzed using 16S rRNA gene high-throughput sequencing and high-performance liquid chromatography-tandem mass spectrometry.

Result: The total average HMO content was significantly higher in the C group than in the S group (6.76 ± 1.40 g/L vs. 10.27 ± 2.00 g/L,  < 0.05). Among the HMOs, the average values of 2'-fucosyllactose (2'-FL, 1.64 ± 1.54 g/L vs. 3.03 ± 1.79 g/L), 3'-sialyllactose (3'-SL, 0.10 ± 0.02 g/L vs. 0.21 ± 0.06), 6'-SL (0.22 ± 0.09 g/L vs. 0.33 ± 0.11 g/L), and lacto-N-triaose 2 (LNT2, 0.03 ± 0.01 g/L vs. 0.16 ± 0.08 g/L) were significantly lower in the S group than in the C group ( < 0.05), while that of 3'-FL was significantly higher in the S group than in the C group (1.35 ± 1.00 g/L vs. 0.41 ± 0.43 g/L,  < 0.05). The diversity and structure of the microbiota in the S and C groups were also significantly different ( < 0.05). Comparative analysis of the microbial communities revealed that Proteobacteria and Firmicutes were the most abundant phyla, in both groups, with the keystone species (, and ) of breast milk closely interacting with HMOs, including 3'-SL, 6'-SL, and LNT2. In PICRUSt2 functional prediction analysis, the S group exhibited significant reduction in the expression of genes involved in several infectious disease pathways.

Discussion: Our findings support the recognition of human milk as a synbiotic comprising beneficial bacteria and prebiotic HMOs.