scholarly journals Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity

2016 ◽  
Vol 69 (Suppl. 2) ◽  
pp. 41-51 ◽  
Author(s):  
Sharon M. Donovan ◽  
Sarah S. Comstock
Keyword(s):  
Human Milk ◽  
Infant Formula ◽  
Bovine Milk ◽  
Complex Mixture ◽  
Structural Diversity ◽  
Host Cells ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Immune Development ◽  
Breastfed Infants

The immune system of the infant is functionally immature and naïve. Human milk contains bioactive proteins, lipids, and carbohydrates that protect the newborn and stimulate innate and adaptive immune development. This review will focus on the role human milk oligosaccharides (HMO) play in neonatal gastrointestinal and systemic immune development and function. For the past decade, intense research has been directed at defining the complexity of oligosaccharides in the milk of many species and is beginning to delineate their diverse functions. These studies have shown that human milk contains a higher concentration as well as a greater structural diversity and degree of fucosylation than the milk oligosaccharides in other species, particularly bovine milk from which many infant formulae are produced. The commercial availability of large quantities of certain HMO has furthered our understanding of the functions of specific HMO, which include protecting the infant from pathogenic infections, facilitating the establishment of the gut microbiota, promoting intestinal development, and stimulating immune maturation. Many of these actions are exerted through carbohydrate-carbohydrate interactions with pathogens or host cells. Two HMOs, 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT), have recently been added to infant formula. Although this is a first step in narrowing the compositional gap between human milk and infant formula, it is unclear whether 1 or 2 HMO will recapitulate the complexity of actions exerted by the complex mixture of HMO ingested by breastfed infants. Thus, as more HMO become commercially available, either isolated from bovine milk or chemically or microbially synthesized, it is anticipated that more oligosaccharides will be added to infant formula either alone or in combination with other prebiotics.

scholarly journals Human Milk Oligosaccharides: The Journey Ahead

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Chandan Ray ◽  
Joshi A. Kerketta ◽  
Subhash Rao ◽  
Snehal Patel ◽  
Shantanu Dutt ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Current Knowledge ◽  
Biological Fluid ◽  
Structural Diversity ◽  
Host Cells ◽  
Future Research ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Signalling Molecules

Breast milk is a complex biological fluid that is rich in nutrients and bioactive agents that support the healthy growth and development of the newborns. Human milk oligosaccharides (HMOs) are unconjugated glycans that constitute an important component of the protection conferred by breast milk on the neonate. HMOs may act locally on the neonatal intestine by acting as signalling molecules and directly interacting with the host cells. Although fucosylated and sialylated HMOs have little nutritional value, they exert important prebiotic as well as immunomodulatory effects on the infant gut. However, there is heterogeneity in the quantity and quality of HMOs in breast milk produced by mothers under influence of the genetic and environmental factors. This review encompasses the salient aspects of HMOs such as composition, function, structural diversity, and functional impact on the growth and survival of newborns. In this review, the current knowledge on HMOs is contextualised to discuss the gaps in scientific understanding and the avenues for future research.

Diversification of a fucosyllactose transporter within the genus Bifidobacterium

2021 ◽  
Author(s):  
Miriam N. Ojima ◽  
Yuya Asao ◽  
Aruto Nakajima ◽  
Toshihiko Katoh ◽  
Motomitsu Kitaoka ◽  
...  
Keyword(s):  
Human Milk ◽  
Binding Proteins ◽  
Heterologous Gene Expression ◽  
Metagenomic Data ◽  
Dependent Manner ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Formula Milk ◽  
Breastfed Infants ◽  
Strain Dependent

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO-assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose (FL)), are associated with the formation of a bifidobacteria-rich gut microbial community. Phylogenetic analysis has revealed that FL transporters have diversified into two clades harboring four clusters within the Bifidobacterium genus, but the underpinning functional diversity associated with this divergence remains underexplored. In this study, we examined the HMO-consumption phenotypes of two bifidobacterial species, Bifidobacterium catenulatum subspecies kashiwanohense and Bifidobacterium pseudocatenulatum , which both possess FL binding proteins that belong to phylogenetic clusters with unknown specificities. Growth assays, heterologous gene expression experiments, and HMO-consumption analysis showed that the FL transporter type from B. catenulatum subspecies kashiwanohense JCM 15439 T conferred a novel HMO-uptake pattern that includes the complex fucosylated HMOs (lacto- N- fucopentaose II and lacto- N- difucohexaose I/II). Further genomic landscape analyses of FL transporter-positive bifidobacterial strains revealed that H-antigen or Lewis antigen-specific fucosidase gene(s) and FL transporter specificities were largely aligned. These results suggest that bifidobacteria have acquired FL transporters along with the corresponding gene sets necessary to utilize the imported HMOs. Our results provide insight into the species- and strain-dependent adaptation strategies of bifidobacteria to HMO-rich environments. Importance The gut of breastfed infants is generally dominated by health-promoting bifidobacteria. Human milk oligosaccharides (HMOs) from breastmilk selectively promote the growth of specific taxa such as bifidobacteria, thus forming an HMO-mediated, host-microbe symbiosis. While the co-evolution of humans and bifidobacteria has been proposed, the underpinning adaptive strategies employed by bifidobacteria require further research. Here, we analyzed the divergence of the critical fucosyllactose (FL) HMO transporter within Bifidobacterium . We have shown that the diversification of the solute-binding proteins of the FL-transporter led to uptake specificities of fucosylated sugars ranging from simple trisaccharides to complex hexasaccharides. This transporter and the congruent acquisition of the necessary intracellular enzymes allows for bifidobacteria to import different types of HMOs in a predictable and strain-dependent manner. These findings explain the adaptation and proliferation of bifidobacteria in the competitive and HMO-rich infant gut environment and enable accurate specificity annotation of transporters from metagenomic data.

scholarly journals Relationship between human milk oligosaccharides and fecal microbiome of breastfed infants

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Janet E Williams ◽  
Mara A Riley ◽  
Sarah L Brooker ◽  
Katherine M Hunt ◽  
Alexandra Szyszka ◽  
...  
Keyword(s):  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Fecal Microbiome ◽  
Breastfed Infants

scholarly journals Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity

2017 ◽  
Vol 64 (4) ◽  
pp. 624-631 ◽  
Author(s):  
Giuseppe Puccio ◽  
Philippe Alliet ◽  
Cinzia Cajozzo ◽  
Elke Janssens ◽  
Giovanni Corsello ◽  
...  
Keyword(s):  
Human Milk ◽  
Infant Formula ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides

Synthesis and biological relevance of N-acetylglucosamine-containing oligosaccharides

2007 ◽  
Vol 79 (12) ◽  
pp. 2229-2242 ◽  
Author(s):  
El Sayed H. El Ashry ◽  
Mohamed R. E. Aly
Keyword(s):  
Human Milk ◽  
Biological Significance ◽  
Structural Diversity ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Biological Relevance ◽  
Glycosidic Bonds ◽  
Synthetic Approaches

The structural diversity as well as the biological significance of N-acetylglucosamine-containing glycans are exemplified. The problem of forming the respective glycosidic bonds of synthetic targets is addressed. Special emphasis has been given to human milk oligosaccharides (HMOs), in view of their biological relevance, and synthetic approaches of selected examples are reported.

scholarly journals Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1030 ◽  
Author(s):  
Marcia H. Monaco ◽  
Dae Hee Kim ◽  
Rit B. Gurung ◽  
Sharon M. Donovan
Keyword(s):  
Human Milk ◽  
Infant Formula ◽  
Sodium Salt ◽  
Large Scale ◽  
Hematological Parameters ◽  
Bovine Milk ◽  
Milk Replacer ◽  
Milk Oligosaccharides ◽  
Neonatal Piglets ◽  
Dose Dependent

Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented to infant formula, however, not all forms have been available in large scale. The objective of the study was to investigate the dose-dependent effects of an enzymatically-synthesized 6′-sialyllactose (6′-SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters, and organ microscopic assessment in our pre-clinical neonatal pig model. Two-day-old male and female pigs (n = 47) were provided one of four experimental diets for 21 days. Diets were formulated to contain 0 (CON), 300 (LOW), 600 (MOD), or 1200 (HIGH) mg/L of 6′-SL sodium salt. On days 8 and 22, samples were collected for hematological and histological analyses. Supplemental 6′-SL sodium salt at all doses supported growth and development comparable to those observed in control animals. In addition, serum chemistries, hematology, and organ microscopic structure were unaffected by 6′-SL (p > 0.05). Thus, addition of enzymatically-synthesized 6′-SL to a milk replacer formula supported growth and clinical outcomes similar to the control formula in the neonatal piglet.

scholarly journals Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria

2016 ◽  
Vol 82 (12) ◽  
pp. 3622-3630 ◽  
Author(s):  
Sercan Karav ◽  
Annabelle Le Parc ◽  
Juliana Maria Leite Nobrega de Moura Bell ◽  
Steven A. Frese ◽  
Nina Kirmiz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Milk ◽  
Bifidobacterium Longum ◽  
Bovine Milk ◽  
Selective Growth ◽  
Whey Protein Concentrate ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Content Type ◽  
Growth Substrates

ABSTRACTMilk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intactN-linked glycans. We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. We demonstrated that EndoBI-1 releasedN-glycans from concentrated bovine colostrum at the pilot scale. EndoBI-1-releasedN-glycans supported the rapid growth ofBifidobacterium longumsubsp.infantis(B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth ofBifidobacterium animalissubsp.lactis(B. lactis), a species which does not. Conversely,B. infantisATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. Mass spectrometry-based profiling revealed thatB. infantisconsumed 73% of neutral and 92% of sialylatedN-glycans, whileB. lactisdegraded only 11% of neutral and virtually no (<1%) sialylatedN-glycans. These results provide mechanistic support thatN-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. Moreover, releasedN-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. Finally, the variety ofN-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides.IMPORTANCEIt has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. In this study, we used a novel enzyme to cleave conjugatedN-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. The results showed that the glycans selectively stimulated the growth ofB. infantis, which is a key infant gut microbe. The selectivity of consumption of individualN-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip–quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal thatB. infantiscan consume the range of glycan structures released from whey protein concentrate.

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

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinzhi Lang ◽  
Yongzhen Zhang ◽  
Chen Wang ◽  
Limei Huang ◽  
Xiaoxiao Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Milk ◽  
Biological Activities ◽  
Complex Mixture ◽  
Molecular Ions ◽  
Quantitative Detection ◽  
Human Milk Oligosaccharides ◽  
Combination Strategy ◽  
Milk Oligosaccharides ◽  
Chromatography Mass Spectrometry

Human milk oligosaccharides (HMOs) exhibit various biological activities for infants, such as serving as prebiotics, blocking pathogens, and aiding in brain development. HMOs are a complex mixture of hetero-oligosaccharides that are generally highly branched, containing multiple structural isomers and no intrinsic chromophores, presenting a challenge to both their resolution and quantitative detection. While liquid chromatography-mass spectrometry (LC-MS) has become the primary strategy for analysis of various compounds, the very polar and chromophore-free properties of native glycans hinder their separation in LC and ionization in MS. Various labeling approaches have been developed to achieve separation of glycans with higher resolution and greater sensitivity of detection. Here, we compared five commonly used labeling techniques [by 2-aminobenzamide, 2-aminopyridine, 2-aminobenzoic acid (2-AA), 2,6-diaminopyridine, and 1-phenyl-3-methyl-5-pyrazolone] for analyzing HMOs specifically under hydrophilic-interaction chromatography-mass spectrometry (HILIC-MS) conditions. The 2-AA labeling showed the most consistent deprotonated molecular ions, the enhanced sensitivity with the least structural selectivity, and the sequencing-informative tandem MS fragmentation spectra for the widest range of HMOs; therefore, this labeling technique was selected for further optimization under the porous graphitized carbon chromatography-mass spectrometry (PGC-MS) conditions. The combination strategy of 2-AA labeling and PGC-MS techniques provided online decontamination (removal of excess 2-AA, salts, and lactose) and resolute detection of many HMOs, enabling us to characterize the profiles of complicated HMO mixtures comprehensively in a simple protocol.

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