Introduction: Breast Milk (BM), containing nutrients and bioactive components, represents the best source for neonatal nutrition and determines short- and long- term benefits. Human milk oligosaccharides (HMOs) play an active role in these pathophysiological mechanisms. In fact, they influence the shaping of breastfed infant’s gut microbiota, promote intestinal development, confer protection against intestinal or systemic infections modulating immune system; moreover, HMOs determine extra-intestinal effects on several target organs, i.e reducing necrotizing enterocolitis rate or improving brain development.
Aims: In this review, we analyze the great inter- and intra-individual variability of BM HMOs, investigating maternal, genetic and environmental factors modulating their composition. Moreover, we provide an update regarding HMOs’ unique properties, underlining their complex interaction with intestinal microbiota and host-derived metabolites. The possible HMOs’ influence on extraintestinal bacterial communities, potentially influencing newborns’ and even lactating mothers’ health, have been hypothesized. Finally, recognized HMOs’ crucial role, we underline the promising opportunities showed by their addition in formula milk, to make it more similar to maternal milk itself.