Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides

Bruggencate, Sandra J. M. Ten; Bovee‐Oudenhoven, Ingeborg M. J.; Feitsma, Anouk L.; Hoffen, Els van; Schoterman, Margriet H. C.

doi:10.1111/nure.12106

Cited by 157 publications

(126 citation statements)

References 169 publications

(381 reference statements)

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“…Both fucosylation and sialylation play significant roles in those functions (Bode and Jantscher-Krenn, 2012; Charbonneau et al, 2016), whereas sialylated OS are essential for neuronal development (ten Bruggencate et al, 2014). Given that PMO are structurally closer to HMO than to BMO, it is interesting to consider whether milk OS are tailor-made for the postnatal development of the specific type of animal gastrointestinal system and, thus, the more similar the gastrointestinal systems are, the closer their milk OS compositions will be (Albrecht et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…Despite OS being the third most abundant components in milk (Kunz et al, 2000), it was long thought they had no biological significance. Recent studies pointed out many and diverse biological activities afforded by milk OS, including prebiotic activity, antiadhesion effects, anti-inflammatory properties, glycome-modifying activity, and roles in brain development, as well as influencing the growth-related characteristics of intestinal cells (Hickey, 2012; Lane et al, 2012; ten Bruggencate et al, 2014). Taken together, these bioactivities favor the establishment of a protective and healthful intestinal environment (Smilowitz et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome

salcedo

Frese

Mills

et al. 2016

Journal of Dairy Science

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The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA). Previously sequenced metagenome libraries were reanalyzed to examine changes with specific gut bacterial populations. Over 30 oligosaccharides (OS) were identified in the milk, with 3′-sialyllactose, lacto-N-tetraose, α1–3,β1–4-d-galactotriose, 2′-fucosyllactose, and 6′-sialyllactose being the most abundant species (accounting for ~70% of the total OS). Porcine milk had lower OS diversity (number of unique structures) than human milk, and appeared closer to bovine and caprine milk. In agreement with previous studies, only 3 fucosylated OS were identified. Surprisingly, their contribution to total OS abundance was greater than in bovine milk (9 vs. 1%). Indeed, fucosylated PMO increased during lactation, mirroring a similar trend observed for neutral and type I OS content during early lactation. Taken together, these results suggest that, in terms of abundance, PMO are closer to human milk than other domestic species, such as bovine and caprine milks. Metagenomic sequencing revealed that fucose-consuming bacterial taxa in the gut microbiota of piglets were qualitatively but not quantitatively different between nursing and weaning stages, suggesting that both the composition and structure of dietary glycans may play a critical role in shaping the distal gut microbiome. The similarity of both intestinal physiopathology and milk OS composition in human and porcine species suggests similar effects on gastrointestinal development of early nutrition, reinforcing the use of the pig intestinal model to simulate human intestinal models in the clinical setting.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome

salcedo

Frese

Mills

et al. 2016

Journal of Dairy Science

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“…The sialyllactoses contribute significantly to the biomass of acidic HMOs. As much as 0.25 to 0.6 g/L of breastmilk is documented to be made up of 3′-sialyllactose sodium salt (3′-SL) alone (Ten Bruggencate et al, 2014). Sialylated HMOs exhibit a variety of biological functions that the neutral HMO fraction cannot provide completely on its own (Ten Bruggencate et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Toxicological safety assessment of the human‐identical milk oligosaccharide 3′‐sialyllactose sodium salt

Phipps

Baldwin

Lynch

et al. 2019

J of Applied Toxicology

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Human breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3′‐sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human‐identical milk oligosaccharides (structurally identical to HMOs) such as 3′‐sialyllactose sodium salt (3′‐SL) are proposed for use in IF and foods for the general population. The safety assessment of 3′‐SL comprised in vitro genotoxicity tests and a 90‐day oral (gavage) toxicity study. This is the first 90‐day study conducted with 3′‐SL using neonatal rats (7 days old at the start of dosing—equivalent age to newborn human infants in terms of central nervous system and reproductive development), demonstrating the safety of 3′‐SL for consumption by infants, the most sensitive age group. The neonatal rats received 3′‐SL at doses up to 5,000 mg/kg body weight (BW)/day and reference controls received 5,000 mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in IF) for comparison with the high‐dose 3′‐SL group, followed by a 4‐week recovery period. There was no evidence of genotoxicity in vitro. In the absence of any test item‐related adverse effects in the 90‐day study, the high dose (5,000 mg/kg BW/day) was established as the no‐observed‐adverse‐effect level. This confirms the safety of 3′‐SL for use in IF for infants, as well as in functional foods for the general population.

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“…The content of Sialylated HMOs is high in colostrum (1500 mg/L) and decreases in mature milk (to 300 mg/L) (Ten Bruggencate, Bovee-Oudenhoven, Feitsma, van Hoffen, & Schoterman, 2014). The concentrations of acid oligosaccharides have been found to be not dependent on the Lewis blood group, and sialyltransferases are found broadly distributed in all human cells, including those of the lactating mammary gland (Maksimovic, Sharp, Nicholas, Cocks, & Savin, 2011).…”

Section: Maternal Factorsmentioning

confidence: 99%

Relationship Between Oligosaccharides and Glycoconjugates Content in Human Milk and the Development of the Gut Barrier

Figueroa-Lozano

Vos

2018

Comp Rev Food Sci Food Safe

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The intestinal immune barrier is considered to be the gatekeeper of the human body and rapidly develops directly after birth. Many pre‐ and postnatal factors influence the development of the gut‐barrier, which is composed of the microbiota, the mucus, the epithelial layer and the mucosal immune system. Even minor disturbances during barrier development can have consequences for health far into adulthood. Here we critically discuss the current knowledge on which pre‐ and postnatal factors influence development, maturation, and maintenance of the gut immune barrier. Human milk has a unique composition and is the gold standard for adequate development of the intestinal immune barrier. Not only the influence of human milk oligosaccharides (HMOs) but also that of glycoproteins (HMGPs) is reviewed. We discuss the influence of maternal genetic factors, such as the secretor and Lewis phenotypes on breast milk fucosylation and sialylation of HMOs and HMGPs. This diversity in HMOs and HMPGs influences microbiota composition and also the development of the immune barrier. Cow milk‐derived infant formula is often being used as an alternative for human breast milk. The consequences of this for proper development of the intestinal immune barrier and, in particular, the differences in the type of oligosaccharides and glycosylation patterns (sialic and fucose composition) between cow and human milk are critically discussed. Current and prospective strategies to promote proper gut‐immune maturation are proposed. These might include more personalized infant formulas when breast milk is not an option.

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Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides

Cited by 157 publications

References 169 publications

Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome

Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome

Toxicological safety assessment of the human‐identical milk oligosaccharide 3′‐sialyllactose sodium salt

Relationship Between Oligosaccharides and Glycoconjugates Content in Human Milk and the Development of the Gut Barrier

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