Current Perspective of Sialylated Milk Oligosaccharides in Mammalian Milk: Implications for Brain and Gut Health of Newborns

Abstract

Human milk oligosaccharides (HMOs) are the third most abundant solid component after lactose and lipids of breast milk. All mammal milk contains soluble oligosaccharides, including neutral milk oligosaccharides (NMOs) without sialic acid (Sia) moieties and acidic oligosaccharides or sialylated milk oligosaccharides (SMOs) with Sia residues at the end of sugar chains. The structural, biological diversity, and concentration of milk oligosaccharides in mammalian milk are significantly different among species. HMOs have multiple health benefits for newborns, including development of immune system, modification of the intestinal microbiota, anti-adhesive effect against pathogens, and brain development. Most infant formulas lack oligosaccharides which resemble HMOs. Formula-fed infants perform poorly across physical and psychological wellbeing measures and suffer health disadvantages compared to breast-fed infants due to the differences in the nutritional composition of breast milk and infant formula. Of these milk oligosaccharides, SMOs are coming to the forefront of research due to the beneficial nature of Sia. This review aims to critically discuss the current state of knowledge of the biology and role of SMOs in human milk, infant formula milks, and milk from several other species on gut and brain health of human and animal offspring.

Studies and Application of Sialylated Milk Components on Regulating Neonatal Gut Microbiota and Health

“…Sialylated HMOs are mainly composed of 3 ′ -sialyllactose (3 ′ -SL), 6 ′ -sialyllactose (6 ′ -SL), LS-tetra-saccharide a (LSTa), LS-tetra-saccharide b (LSTb), LS-tera-saccharide c (LSTc), and disialyllacto-N-tetraose (DSLNT) (17, 18) (Figure 2A), and the concentration of them is about 1,000-3,300 mg/L in the colostrum and droped to about 135-2,150 mg/L in the matured human milk (Table 1). Among all sialylated HMOs, the content of sialyllactose (SL) is the highest, with an estimated concentration of 170-500 µg/mL for 6 ′ -SL in mature breast milk (6,(22)(23)(24). SL play important roles in neonatal gut maturation, prevention of pathogen invasion, immune regulation, and prebiotic function (33).…”

Exposure to 3′Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood

“…Additional evidence in favor of the role of HMOs in the development of cognitive capabilities stems from the observation that genetic polymorphisms leading to variations in HMO concentrations relate to differential development of the receptive and expressive domains of language in children [25]. The evolutionary preserved role of HMOs is highlighted by the presence of these constituents in many diverse mammalian species [6,26]. The relative concentration of these constituents has been shown to considerably fluctuate among different species (see [26][27][28]), with donkey milk attaining particularly elevated concentrations of sialylated oligosaccharides compared to other species [29].…”

“…The evolutionary preserved role of HMOs is highlighted by the presence of these constituents in many diverse mammalian species [6,26]. The relative concentration of these constituents has been shown to considerably fluctuate among different species (see [26][27][28]), with donkey milk attaining particularly elevated concentrations of sialylated oligosaccharides compared to other species [29].…”

Comparison of Different Labeling Techniques for the LC-MS Profiling of Human Milk Oligosaccharides

“…Another comparison on the small trisaccharides ( Figure 3B ) however revealed that 2-AA derivatization had an additional specific loss of sialylated lactose (SL) series (0-2-0-1) compared with other labeling methods. The SL series are the most abundant components of acidic HMOs and have become a hot spot in HMO biology research ( Weiss and Hennet, 2012 ; Kurakevich et al, 2013 ; Moon et al, 2016 ; Hobbs et al, 2021 ).…”