Human Milk Oligosaccharides in Nutrition and Health: the past, present, and future

Abstract Human milk is considered the most appropriate and balanced form of nutrition for infants, and remains the sole recommended source of nourishment during the newborn period. Beyond its role in supplying essential nutrients, human milk naturally contains a complex mixture of biologically active substances that contribute to infant growth, immune protection, and overall health. Among these components, human milk oligosaccharides (HMOs) stand out for both their abundance and structural diversity. Found exclusively and in high concentrations in human milk, HMOs function as prebiotic molecules that are not digested by human enzymes. Instead, they foster the colonization of beneficial intestinal microbes, block the attachment of pathogens to epithelial surfaces, influence gut and immune signaling pathways, and have been linked to favorable effects on brain development and cognitive performance in early life. In this review, we first trace the historical progression of HMO research and summarize the key milestones in studies conducted domestically and internationally. We then summarized the preclinical and clinical data on HMOs over the past decade. Finally, we highlighted the recent progress in the synthesis and production of HMOs, as well as current understanding of their metabolic utilization by the infant gut microbiota during breastfeeding. Overall, HMOs serve as key bioactive factors supporting infant nutrition, microbial balance, and immune protection. Therefore, breastfeeding remains the most natural and effective approach to deliver these functional components and promote healthy growth and development in early life.