Food for Thought: How Human Milk Oligosaccharides contribute to neural plasticity and cognitive development throughout the lifespan

Breast milk is considered the gold standard for infant nutrition because it provides both essential nutrients and bioactive components that shape growth, the gut microbiota and immune function. When breastfeeding is not possible, infant formula is a complete alternative, but it still differs from breast milk in key ways, especially in its limited set of Human Milk Oligosaccharides (HMOs). Breast milk contains over 150 HMOs, and their amounts and ratios vary with lactation stage and maternal factors, suggesting a dynamic, individualized profile that formula does not yet match. Evidence from animal work links fucosylated and sialylated HMOs to neurodevelopment, affecting the medial prefrontal cortex and hippocampus through microbiome-driven metabolites that regulate genes involved in plasticity, myelination and memory. To test whether HMOs act synergistically, a longitudinal rat study administered 2-FL, 3-SL, 6-SL and their combinations from postnatal day 8–49, tracking physical milestones and emotional/cognitive behaviour into adulthood. Different mixtures produced distinct developmental and anxiety/exploration profiles, with notable sex-dependent effects, and a triple mix improving object-recognition memory in adult males alongside altered medial prefrontal cortex gene expression and hippocampal neurogenesis.