Vitamin D and its role in human milk oligosaccharide production.

INTRODUCTION

Human milk oligosaccharides (HMOs) arise from tightly regulated glycosylation pathways and exert pleiotropic effects on infant immune, microbial, and neurodevelopmental trajectories. Vitamin D influences gene transcription and cellular metabolism, yet its potential role in mammary glycosylation remains unexplored. We examined whether maternal vitamin D status during lactation is associated with HMO composition and whether effects vary by maternal secretor phenotype.

METHODS

We performed a post hoc analysis of two clinical studies: the NICHD vitamin D lactation randomized controlled trial (2005-2012) and the Lactation Immune Trial pilot (n = 88). Serum 25-hydroxyvitamin D [25(OH)D, vitamin D status] and 19 HMOs concentrations were measured at 1 and 4 months postpartum. Secretor status was defined by presence of 2'-fucosyllactose. Statistical analyses were conducted using SAS 9.4 with p < 0.05.

RESULTS

The cohort comprised 41% White, 7% Black, and 52% Hispanic women. Black and Hispanic mothers exhibited lower 25(OH)D concentrations than White mothers (p < 0.001), and Hispanic mothers were more likely to be secretors (p = 0.006). In secretors, higher 25(OH)D was significantly associated with increased fucosylated and complex HMOs, including lacto-N-fucopentaose II, lacto-N-hexaose, and fucosyl-disialyl-lacto-N-hexaose I at 1 month, with sustained association for the latter at 4 months. In non-secretors, higher 25(OH)D was associated with lower 6'-sialyllactose at 4 months. Distinct HMO patterns were observed by secretor phenotype.

CONCLUSION

Vitamin D status is associated with differential HMO profiles during early lactation, supporting a potential role for vitamin D-mediated regulation of mammary glycosylation that is modified by secretor status.