Breast milk is the gold standard in infant nutrition. In addition to provide essential nutrients for the newborn, it contains multiple bioactive molecules that provide protection and stimulate proper development. Human milk oligosaccharides (HMO) are complex carbohydrates abundant in breast milk. Intriguingly, these molecules do not provide energy to the infant. Instead, these oligosaccharides are key to guide and support the assembly of a healthy gut microbiome in the infant, dominated by beneficial gut microbes such as Bifidobacterium. New analytical methods for glycan analysis, and next-generation sequencing of microbial communities, have been instrumental in advancing our understanding of the positive role of breast milk oligosaccharides on the gut microbiome, and the genomics and molecular strategies of Bifidobacterium to utilize these oligosaccharides. Moreover, novel approaches to simulate the impact of HMO on the gut microbiome have been described and successfully validated, including the incorporation of synthetic HMO and bovine milk oligosaccharides to infant formula. This review discusses recent advances regarding the influence of HMO in promoting a healthy gut microbiome, with emphasis in the molecular basis of the enrichment in beneficial Bifidobacterium, and novel approaches to replicate the effect of HMO using synthetic or bovine oligosaccharides.
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