scholarly journals More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

2020 ◽  
pp. 1-17 ◽  
Author(s):  
Lianghui Cheng ◽  
Renate Akkerman ◽  
Chunli Kong ◽  
Marthe T. C. Walvoort ◽  
Paul de Vos
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Bioactive Molecules ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Beneficial Effects

scholarly journals Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode

2021 ◽  
Author(s):  
Jonas Hauser ◽  
Edoardo Pisa ◽  
Alejandro Arias Vásquez ◽  
Flavio Tomasi ◽  
Alice Traversa ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Gut Microbiota ◽  
Human Milk ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Nervous System Development ◽  
Bioactive Molecules ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Eye Opening

AbstractBreastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

scholarly journals Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1556 ◽  
Author(s):  
Erik Wejryd ◽  
Magalí Martí ◽  
Giovanna Marchini ◽  
Anna Werme ◽  
Baldvin Jonsson ◽  
...  
Keyword(s):  
Birth Weight ◽  
Breast Milk ◽  
Low Birth Weight ◽  
Human Milk ◽  
Amperometric Detection ◽  
Exchange Chromatography ◽  
Extremely Low Birth Weight ◽  
Human Milk Oligosaccharides ◽  
Low Birth Weight Infants ◽  
Milk Oligosaccharides

Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; <1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3′-sialyllactose and 6′-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

scholarly journals Efforts to emulate human milk oligosaccharides

2007 ◽  
Vol 98 (S1) ◽  
pp. S74-S79 ◽  
Author(s):  
Rosa María Espinosa ◽  
Martha Taméz ◽  
Pedro Prieto
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Current Knowledge ◽  
Biological Effects ◽  
Historical Context ◽  
Published Data ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Fast Analysis ◽  
Chemical Structures

Research on human milk oligosaccharides (HMO) began with the characterisation of their chemical structures and is now focused on the elucidation of their biological roles. Previously, biological effects could only be investigated with fractions or structures isolated from breast milk; consequently, clinical observations were limited to comparisons between outcomes from breast-fed infants and their formula-fed counterparts. In some cases, it was inferred that the observed differences were caused by the presence of HMO in breast milk. Presently, analytical techniques allow for the fast analysis of milk samples, thus providing insights on the inherent variability of specimens. In addition, methods for the synthesis of HMO have provided single structures in sufficient quantities to perform clinical studies with oligosaccharide-supplemented formulae. Furthermore, studies have been conducted with non-mammalian oligosaccharides with the purpose of assessing the suitability of these structures to functionally emulate HMO. Taken together, these developments justify summarising current knowledge on HMO to further discussions on efforts to emulate human milk in regard to its oligosaccharide content. The present account summarises published data and intends to provide an historical context and to illustrate the state of the field.

scholarly journals New strategies for profiling and characterization of human milk oligosaccharides

Glycobiology ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 774-786 ◽  
Author(s):  
Sara Porfirio ◽  
Stephanie Archer-Hartmann ◽  
G Brett Moreau ◽  
Girija Ramakrishnan ◽  
Rashidul Haque ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Milk Composition ◽  
Human Breast Milk ◽  
Human Milk Oligosaccharides ◽  
Bacterial Strains ◽  
Milk Oligosaccharides ◽  
Vast Number ◽  
The Impact

Abstract Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being &gt;5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.

scholarly journals Influence of sulfonated and diet-derived human milk oligosaccharides on the infant microbiome and immune markers

2020 ◽  
Vol 295 (12) ◽  
pp. 4035-4048 ◽  
Author(s):  
Candice Quin ◽  
Sara D. Vicaretti ◽  
Nina A Mohtarudin ◽  
Alexander M. Garner ◽  
Deanna M. Vollman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Breast Milk ◽  
Human Milk ◽  
Unsaturated Fatty Acids ◽  
Maternal Diet ◽  
Intestinal Microbiome ◽  
Human Milk Oligosaccharides ◽  
Immune Markers ◽  
Milk Oligosaccharides ◽  
Milk Fatty Acids

Human milk oligosaccharides (HMOs) promote the development of the neonatal intestinal, immune, and nervous systems and has recently received considerable attention. Here we investigated how the maternal diet affects HMO biosynthesis and how any diet-induced HMO alterations influence the infant gut microbiome and immunity. Using capillary electrophoresis and MS-based analyses, we extracted and measured HMOs from breast milk samples and then correlated their levels with results from validated 24-h diet recall surveys and breast milk fatty acids. We found that fruit intake and unsaturated fatty acids in breast milk were positively correlated with an increased absolute abundance of numerous HMOs, including 16 sulfonated HMOs we identified here in humans for the first time. The diet-derived monosaccharide 5-N-glycolyl-neuraminic acid (Neu5Gc) was unambiguously detected in all samples. To gain insights into the potential impact of Neu5Gc on the infant microbiome, we used a constrained ordination approach and identified correlations between Neu5Gc levels and Bacteroides spp. in infant stool. However, Neu5Gc was not associated with marked changes in infant immune markers, in contrast with sulfonated HMOs, whose expression correlated with suppression of two major Th2 cytokines, IL-10 and IL-13. The findings of our work highlight the importance of maternal diet for HMO biosynthesis and provide as yet unexplored targets for future studies investigating interactions between HMOs and the intestinal microbiome and immunity in infants.

scholarly journals Human milk oligosaccharides reduceEntamoeba histolyticaattachment and cytotoxicityin vitro

2012 ◽  
Vol 108 (10) ◽  
pp. 1839-1846 ◽  
Author(s):  
Evelyn Jantscher-Krenn ◽  
Tineke Lauwaet ◽  
Laura A. Bliss ◽  
Sharon L. Reed ◽  
Frances D. Gillin ◽  
...  
Keyword(s):  
Human Milk ◽  
Protozoan Parasite ◽  
Bacterial Attachment ◽  
Dependent Manner ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Beneficial Effects ◽  
Ht 29

Human milk oligosaccharides (HMO), complex sugars that are highly abundant in breast milk, block viral and bacterial attachment to the infant's intestinal epithelium and lower the risk of infections. We hypothesised that HMO also prevent infections with the protozoan parasiteEntamoeba histolytica,as its major virulence factor is a lectin that facilitates parasite attachment and cytotoxicity and binds galactose (Gal) andN-acetyl-galactosamine. HMO contain Gal, are only minimally digested in the small intestine and reach the colon, the site ofE. histolyticainfection. The objective of the present study was to investigate whether HMO reduceE. histolyticaattachment and cytotoxicity. Ourin vitroresults show that physiological concentrations of isolated, pooled HMO detachE. histolyticaby more than 80 %. In addition, HMO rescueE. histolytica-induced destruction of human intestinal epithelial HT-29 cells in a dose-dependent manner. The cytoprotective effects were structure-specific. Lacto-N-tetraose with its terminal Gal rescued up to 80 % of the HT-29 cells, while HMO with fucose α1–2-linked to the terminal Gal had no effect. Galacto-oligosaccharides (GOS), which also contain terminal Gal and are currently added to infant formula to mimic some of the beneficial effects of HMO, completely abolishedE. histolyticaattachment and cytotoxicity at 8 mg/ml. Although our results need to be confirmedin vivo, they may provide one explanation for why breast-fed infants are at lower risk ofE. histolyticainfections. HMO and GOS are heat tolerant, stable, safe and in the case of GOS, inexpensive, which could make them valuable candidates as alternative preventive and therapeutic anti-amoebic agents.

scholarly journals Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 804
Author(s):  
Laura Corona ◽  
Anna Lussu ◽  
Alice Bosco ◽  
Roberta Pintus ◽  
Flaminia Cesare Marincola ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Genetic Factors ◽  
Environmental Influence ◽  
Protective Role ◽  
Point Of View ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
The Third

Human milk oligosaccharides (HMOs) are the third most represented component in breast milk. They serve not only as prebiotics but they exert a protective role against some significant neonatal pathologies such as necrotizing enterocolitis. Furthermore, they can program the immune system and consequently reduce allergies and autoimmune diseases’ incidence. HMOs also play a crucial role in brain development and in the gut barrier’s maturation. Moreover, the maternal genetic factors influencing different HMO patterns and their modulation by the interaction and the competition between active enzymes have been widely investigated in the literature, but there are few studies concerning the role of other factors such as maternal health, nutrition, and environmental influence. In this context, metabolomics, one of the newest “omics” sciences that provides a snapshot of the metabolites present in bio-fluids, such as breast milk, could be useful to investigate the HMO content in human milk. The authors performed a review, from 2012 to the beginning of 2021, concerning the application of metabolomics to investigate the HMOs, by using Pubmed, Researchgate and Scopus as source databases. Through this technology, it is possible to know in real-time whether a mother produces a specific oligosaccharide, keeping into consideration that there are other modifiable and unmodifiable factors that influence HMO production from a qualitative and a quantitative point of view. Although further studies are needed to provide clinical substantiation, in the future, thanks to metabolomics, this could be possible by using a dipstick and adding the eventual missing oligosaccharide to the breast milk or formula in order to give the best and the most personalized nutritional regimen for each newborn, adjusting to different necessities.

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