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

Abstract

Breast milk is rich in sialic acids (SA), which are commonly combined with milk oligosaccharides and glycoconjugates. As a functional nutrient component, SA-containing milk components have received increasing attention in recent years. Sialylated human milk oligosaccharides (HMOs) have been demonstrated to promote the growth and metabolism of beneficial gut microbiota in infants, bringing positive outcomes to intestinal health and immune function. They also exhibit antiviral and bacteriostatic activities in the intestinal mucosa of new-borns, thereby inhibiting the adhesion of pathogens to host cells. These properties play a pivotal role in regulating the intestinal microbial ecosystem and preventing the occurrence of neonatal inflammatory diseases. In addition, some recent studies also support the promoting effects of sialylated HMOs on neonatal bone and brain development. In addition to HMOs, sialylated glycoproteins and glycolipids are abundant in milk, and are also critical to neonatal health. This article reviews the current research progress in the regulation of sialylated milk oligosaccharides and glycoconjugates on neonatal gut microbiota and health.

Variations in Oligosaccharides and N/O-Glycans in Human Milk through the Eight-Month Lactation Period

“…As shown in Table S4, 23 N-glycans all share a common core sequence, Manα1−3(Manα1−6)Manβ1−4GlcNAcβ1− 4GlcNAcβ1-Asn-X-Ser/Thr, and could be classified into three types: oligomannose, in which only Man residues extend the core (H5N2, H6N2); complex, in which "antennae" initiated by GlcNAc extend the core (H3N4, H3N5, H5N4-1/ 3, H3N5F1, H5N4F1-1/2/3, H5N4F1A1-1/2); hybrid, in which one branch of the core was extended by Man and another was extended by one or two GlcNAcs (H3N3F1, H4N3-1/2, H4N3F1-1/2/3, H4N3A1, H5N4-2, H4N3F1A1-1/2/3). 57 Besides, it was found that the amount of neutral Nglycans (17) in human milk was greater than that of acidic Nglycans (6); similarly, the amount of fucosylated N-glycans (9) in human milk exceeded that of sialylated N-glycans (6), consistent with previous studies. 32,37,58 The extracted ion chromatogram and the peak area of each N-glycan derivative are shown in Figure S2 and Table S4, respectively, and the peak area was used for quantitative comparison.…”

“…Other than oligosaccharides, glycans in human milk exist in glycoconjugates, principally glycoproteins . Over 70% of human milk proteins, such as lactoferrin, α-lactalbumin, secretory immunoglobulin A, and κ-casein, are thought to be glycosylated. − Glycans are covalently attached to proteins primarily through two types of linkages, N -linked glycosylation and O -linked glycosylation, with the former occurring on asparagine residues and the latter occurring on the side chain of serine or threonine residues …”

Molecular Dynamics Simulations Reveal the Conformational Transition of GH33 Sialidases

“…Human milk oligosaccharides are important nutrition for neonatal growth [ 2 , 24 ]. Sialyloligosaccharides are significant components of HMOs, which may improve intestinal maturation and cognitive development in neonate [ 25 ]. Although sialidases offer a promising strategy to synthesize sialyloligosaccharides, the poor activity often hindered their industrial applications [ 24 ].…”

Supplementing maternal diet with milk oligosaccharides and probiotics helps develop the immune system and intestinal flora of offsprings

“…Reportedly, each Bifidobacterium living in the infant gut and bacteria of other genera use distinct molecular mechanisms to capture and digest differentially structured HMOs to avoid competition, thereby successfully maintaining the dynamic balance of the gut (Salli et al, 2020). In previous studies, the effect of breast milk oligosaccharides on the regulation of gut microbiota was inconsistent (Hu et al, 2023;Wang, Hu, et al, 2021;Wang, Ze, et al, 2021;Zhang et al, 2021). Herein, intervention with 2′-FL alone in pregnant mice significantly increased the abundance of Lactobacillus and Bifidobacteria in the feces of the offspring mice, with the addition of Bifidobacterium Bb12 alone also exhibiting a similar effect.…”

“…Particularly, during early life, the microbiome profoundly influences the development and maturation of the gastrointestinal tract mucosa, which may affect health in later life (Thum et al, 2012). The first bacteria in the gastrointestinal tract of newborns originate from the maternal birth canal and breast milk and the environment (Wampach et al, 2018; Wang, Hu, et al, 2021; Wang, Ze, et al, 2021). Following parturition, bacteria rapidly colonize the relatively sterile gastrointestinal tract of newborns, marking the beginning of the highly complex process of microbiome establishment (Bäckhed et al, 2015; Ray, 2016).…”