scholarly journals Human Milk Oligosaccharides and Immune System Development

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1038 ◽  
Author(s):  
Julio Plaza-Díaz ◽  
Luis Fontana ◽  
Angel Gil
Keyword(s):  
Immune System ◽  
Human Milk ◽  
Intestinal Mucosa ◽  
System Development ◽  
Controlled Trials ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Maternal Milk ◽  
Breastfed Infants ◽  
Immune System Development

Maternal milk contains compounds that may affect newborn immunity. Among these are a group of oligosaccharides that are synthesized in the mammary gland from lactose; these oligosaccharides have been termed human milk oligosaccharides (HMOs). The amount of HMOs present in human milk is greater than the amount of protein. In fact, HMOs are the third-most abundant solid component in maternal milk after lactose and lipids, and are thus considered to be key components. The importance of HMOs may be explained by their inhibitory effects on the adhesion of microorganisms to the intestinal mucosa, the growth of pathogens through the production of bacteriocins and organic acids, and the expression of genes that are involved in inflammation. This review begins with short descriptions of the basic structures of HMOs and the gut immune system, continues with the beneficial effects of HMOs shown in cell and animal studies, and it ends with the observational and randomized controlled trials carried out in humans to date, with particular emphasis on their effect on immune system development. HMOs seem to protect breastfed infants against microbial infections. The protective effect has been found to be exerted through cell signaling and cell-to-cell recognition events, enrichment of the protective gut microbiota, the modulation of microbial adhesion, and the invasion of the infant intestinal mucosa. In addition, infants fed formula supplemented with selected HMOs exhibit a pattern of inflammatory cytokines closer to that of exclusively breastfed infants. Unfortunately, the positive effects found in preclinical studies have not been substantiated in the few randomized, double-blinded, multicenter, controlled trials that are available, perhaps partly because these studies focus on aspects other than the immune response (e.g., growth, tolerance, and stool microbiota).

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 Screening natural libraries of human milk oligosaccharides against lectins using CaR-ESI-MS

The Analyst ◽  
2018 ◽  
Vol 143 (2) ◽  
pp. 536-548 ◽  
Author(s):  
Amr El-Hawiet ◽  
Yajie Chen ◽  
Km Shams-Ud-Doha ◽  
Elena N. Kitova ◽  
Pavel I. Kitov ◽  
...  
Keyword(s):  
Immune System ◽  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Esi Ms ◽  
Protein Receptors ◽  
Non Covalent Interactions ◽  
Protection Against Infection ◽  
Covalent Interactions ◽  
Breast Fed

Human milk oligosaccharides (HMOs) afford many health benefits to breast-fed infants, such as protection against infection and regulation of the immune system, through the formation of non-covalent interactions with protein receptors.

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 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 (HMOs) and Infant Microbiota: A Scoping Review

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1429
Author(s):  
Cristina Sánchez ◽  
Cristina Fente ◽  
Patricia Regal ◽  
Alexandre Lamas ◽  
María Paz Lorenzo
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Mode Of Delivery ◽  
Geographic Location ◽  
Microbial Colonization ◽  
Human Milk Oligosaccharides ◽  
Maternal Factors ◽  
Milk Oligosaccharides ◽  
Breastfed Infants ◽  
The Impact

Human milk oligosaccharides (HMOs) are the third most abundant solid component of breast milk. However, the newborn cannot assimilate them as nutrients. They are recognized prebiotic agents (the first in the newborn diet) that stimulate the growth of beneficial microorganisms, mainly the genus Bifidobacterium, dominant in the gut of breastfed infants. The structures of the oligosaccharides vary mainly according to maternal genetics, but also other maternal factors such as parity and mode of delivery, age, diet, and nutritional status or even geographic location and seasonality cause different breast milk oligosaccharides profiles. Differences in the profiles of HMO have been linked to breast milk microbiota and gut microbial colonization of babies. Here, we provide a review of the scope of reports on associations between HMOs and the infant gut microbiota to assess the impact of HMO composition.

scholarly journals Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents

2021 ◽  
Vol 12 ◽  
Author(s):  
Anaïs Rousseaux ◽  
Carole Brosseau ◽  
Sophie Le Gall ◽  
Hugues Piloquet ◽  
Sébastien Barbarot ◽  
...  
Keyword(s):  
Immune System ◽  
Human Milk ◽  
Molecular Mechanisms ◽  
Bacterial Colonization ◽  
Therapeutic Agents ◽  
Allergy Prevention ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Inflammatory Reactions ◽  
Epithelial Barriers

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.

scholarly journals Human Milk Oligosaccharides in Serum of Breastfed Infants

1999 ◽  
Vol 45 ◽  
pp. 744-744
Author(s):  
G V Coppa ◽  
P Pierani ◽  
L Zampini ◽  
A Carlucci ◽  
S Bruni ◽  
...  
Keyword(s):  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Breastfed Infants

scholarly journals Direct Evidence for the Presence of Human Milk Oligosaccharides in the Circulation of Breastfed Infants

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101692 ◽  
Author(s):  
Karen C. Goehring ◽  
Adam D. Kennedy ◽  
Pedro A. Prieto ◽  
Rachael H. Buck
Keyword(s):  
Human Milk ◽  
Direct Evidence ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Breastfed Infants
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