Structural diversity, composition variation and neurodevelopmental-promoting effects of human milk oligosaccharides: A systematic review

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk, following lactose and fat, and play a crucial role in neonatal development through multiple mechanisms. This review elaborates on the structural diversity of HMOs, encompassing over 200 distinct molecules. These molecules are classified into neutral fucosylated, neutral non-fucosylated, and acidic sialylated types based on their monosaccharide composition and terminal modifications. Furthermore, factors influencing the compositional variation of HMOs are explored, including genetic factors, mode of delivery, geographical and environmental differences, as well as maternal health status. Critically, HMOs can exert a profound impact on neurodevelopment via the “gut-brain axis”. HMOs can modulate the gut microbiota, promoting the proliferation of bifidobacteria, thereby enhancing the integrity of the intestinal barrier and reducing the risk of pathogen invasion, which indirectly protects brain health. Additionally, they directly influence neurotransmitter pathways and the release of neurotrophic factors, facilitating neuronal growth and synaptic plasticity, and thus promoting brain development. Safety assessments confirm that HMOs are suitable for inclusion in infant formula, offering a promising avenue to bridge nutritional gaps in infants when breastfeeding is insufficient.