In Love with Shaping You—Influential Factors on the Breast Milk Content of Human Milk Oligosaccharides and Their Decisive Roles for Neonatal Development

Human milk oligosaccharides (HMOs) are structurally versatile sugar molecules constituting the third major group of soluble components in human breast milk. Based on the disaccharide lactose, the mammary glands of future and lactating mothers produce a few hundreds of different HMOs implicating that their overall anabolism utilizes rather high amounts of energy. At first sight, it therefore seems contradictory that these sugars are indigestible for infants raising the question of why such an energy-intensive molecular class evolved. However, in-depth analysis of their molecular modes of action reveals that Mother Nature created HMOs for neonatal development, protection and promotion of health. This is not solely facilitated by HMOs in their indigestible form but also by catabolites that are generated by microbial metabolism in the neonatal gut additionally qualifying HMOs as natural prebiotics. This narrative review elucidates factors influencing the HMO composition as well as physiological roles of HMOs on their way through the infant body and within the gut, where a major portion of HMOs faces microbial catabolism. Concurrently, this work summarizes in vitro, preclinical and observational as well as interventional clinical studies that analyzed potential health effects that have been demonstrated by or were related to either human milk-derived or synthetic HMOs or HMO fractions.