Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics

Abstract

Human milk oligosaccharides (HMOs) are the third most represented component in breast milk. They serve not only as prebiotics but they exert a protective role against some significant neonatal pathologies such as necrotizing enterocolitis. Furthermore, they can program the immune system and consequently reduce allergies and autoimmune diseases’ incidence. HMOs also play a crucial role in brain development and in the gut barrier’s maturation. Moreover, the maternal genetic factors influencing different HMO patterns and their modulation by the interaction and the competition between active enzymes have been widely investigated in the literature, but there are few studies concerning the role of other factors such as maternal health, nutrition, and environmental influence. In this context, metabolomics, one of the newest “omics” sciences that provides a snapshot of the metabolites present in bio-fluids, such as breast milk, could be useful to investigate the HMO content in human milk. The authors performed a review, from 2012 to the beginning of 2021, concerning the application of metabolomics to investigate the HMOs, by using Pubmed, Researchgate and Scopus as source databases. Through this technology, it is possible to know in real-time whether a mother produces a specific oligosaccharide, keeping into consideration that there are other modifiable and unmodifiable factors that influence HMO production from a qualitative and a quantitative point of view. Although further studies are needed to provide clinical substantiation, in the future, thanks to metabolomics, this could be possible by using a dipstick and adding the eventual missing oligosaccharide to the breast milk or formula in order to give the best and the most personalized nutritional regimen for each newborn, adjusting to different necessities.

Dynamic Changes in the Human Milk Metabolome Over 25 Weeks of Lactation

“…This trend is in line with previous results ( 38 ). Multiple interactions between HMOs and the infant gut microbiota and environment have been extensively reviewed previously ( 6 , 34 , 40 ). Research has suggested that 2-FL and 3-FL are negatively correlated ( 38 ), and studies have demonstrated that both 2-FL and 3-FL promote the growth of infant gut symbionts, enhance production of short chain fatty acids, and improve intestinal mobility and epithelial barrier function ( 6 ).…”

Prebiotics as a Tool for the Prevention and Treatment of Obesity and Diabetes: Classification and Ability to Modulate the Gut Microbiota

“…HMO 2′-fucosyllactose has been identified as the most abundant HMO in breast milk [ 82 ]. Breast milk due to its high levels of 2′-fucosyllactose has shown advantages for the infant because of its efficiency to promote an early high Bifidobacteria -dominated GM [ 83 ]. Several experiments conducted on the supplementation of HMO documented beneficial effects on the overall health of an individual, which includes modification of the GM [ 78 , 81 , 84 ], effects on immune development [ 78 , 85 , 86 ], anti-adhesive antimicrobial effects [ 87 ], and brain development [ 88 , 89 ] ( Table 1 ).…”

Human Milk Oligosaccharides: The New Gold Standard for Premium Infant Formula

“…The HMO pattern in human milk is influenced by the maternal phenotype, health, diet, and geographical distribution. 1 The law and mechanism of the variations in the HMO pattern are current important research topics related to HMOs. For example, the secretor (Se) and Lewis (Le) genes encode α1,2fucosyltransferase and α1,3/4-fucosyltransferase, respectively, and the activation and/or inactivation status of these two enzymes generated by the mother's genotype decide the fucosylated HMO pattern to a great extent.…”

“…For example, the secretor (Se) and Lewis (Le) genes encode α1,2fucosyltransferase and α1,3/4-fucosyltransferase, respectively, and the activation and/or inactivation status of these two enzymes generated by the mother's genotype decide the fucosylated HMO pattern to a great extent. 1 HMOs are indigestible because humans lack the related digestive glycosidases. Instead, the abundant HMOs act as prebiotics to enhance the proliferation of the beneficial microbes and promote the infant intestinal health.…”

“…The different combinations of glucose, galactose, and N -acetylglucosamine constitute different neutral core HMOs, and the core HMOs can be modified to generate fucosylated and/or sialylated HMOs. The HMO pattern in human milk is influenced by the maternal phenotype, health, diet, and geographical distribution . The law and mechanism of the variations in the HMO pattern are current important research topics related to HMOs.…”