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.