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Expert Review of Proteomics 2019: Among the OMICS technologies, that have emerged in recent years, metabolomics has allowed relevant step forwards in clinical research. Several improvements in disease... (Review)
Review
: Among the OMICS technologies, that have emerged in recent years, metabolomics has allowed relevant step forwards in clinical research. Several improvements in disease diagnosis and clinical management have been permitted, even in neonatology. Among potentially evaluable biofluids, breast milk (BM) results are highly interesting, representing a fluid of conjunction between mothers newborns, describing their interaction.: in this review, updating a previous review article, we discuss research articles and reviews on BM metabolomics and found in MEDLINE using metabolomics, breast milk, neonatal nutrition, breastfeeding, human milk composition, and preterm neonates as keywords.: Our research group has a profound interest in metabolomics research. In 2012, we published the first metabolomic analysis on BM samples, reporting interesting data on its composition and relevant differences with formula milk (FM), useful to improve FM composition. As confirmed by successive studies, such technology can detect the specific BM composition and its dependence on several variables, including lactation stage, gestational age, maternal or environmental conditions. Moreover, since BM contaminants or drug levels can be detected, metabolomics also results useful to determine BM safety. These are only a few practical applications of BM analysis, which will be reviewed in this paper.
Topics: Breast Feeding; Female; Humans; Infant Formula; Infant, Newborn; Metabolomics; Milk, Human; Mothers; Nutritional Sciences
PubMed: 31825672
DOI: 10.1080/14789450.2019.1703679 -
Revista Chilena de Pediatria Apr 2018The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development... (Review)
Review
The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development of newborns and infants. Maternal milk supports the growth, adaptation and survival of this immature organism. Recent studies have detected 1606 different proteins in human milk, most of them synthesized in the acini of the glandular tissue while others originate from distant organs such as the lymphoid tissue and the digestive tract. Maternal milk enzymes modify its proteins and liberate peptides with antimicrobial, antihypertensive or stimulatory activities. This proteolytic activity occurs at specific sites in peptide chains. To prevent the extemporaneous activation of these proteolytic enzymes, that would result in inflammatory processes, maternal milk also contains inhibitory peptides that together with the stimulatory peptides conform a complex regulatory system. Some enzymes in maternal milk main tain their activity in the gastrointestinal tract of infants and compensate for the decreased activity of digestive tract enzymes in newborns. Thus, the milk enterokynase stimulates the release of pancreatic proteases as it induces the liberation of cholecystokynin/pancreozymin. The bile salt-activated lipase of human milk is activated in the duodenum by the infants' bile salts and partially compensates for the low levels of pancreatic lipase in newborns. These milk enzymes probably contribute to the nutrition of premature infants as they increase the availability of amino acids and peptides in their upper gastrointestinal tract; furthermore, as their intestinal epithelium is more permeable to peptides and partially digested protein this may help induce immune tolerance. The most relevant issues in the physiology and composition of the maternal milk are presented in this review.
Topics: Biological Evolution; Humans; Mammary Glands, Human; Milk Proteins; Milk, Human; Proteome
PubMed: 29799897
DOI: 10.4067/S0370-41062018000200261 -
Journal of Dairy Science Apr 2020Oligosaccharides are the third most abundant component in human milk. It is widely accepted that they play several important protective, physiological, and biological... (Review)
Review
Oligosaccharides are the third most abundant component in human milk. It is widely accepted that they play several important protective, physiological, and biological roles, including selective growth stimulation of beneficial gut microbiota, inhibition of pathogen adhesion, and immune modulation. However, until recently, very few commercial products on the market have capitalized on these functions. This is mainly because the quantities of human milk oligosaccharides required for clinical trials have been unavailable. Recently, clinical studies have tested the potential beneficial effects of feeding infants formula containing 2'-fucosyllactose, which is the most abundant oligosaccharide in human milk. These studies have opened this field for further well-designed studies, which are required to fully understand the role of human milk oligosaccharides. However, one of the most striking features of human milk is its diversity of oligosaccharides, with over 200 identified to date. It may be that a mixture of oligosaccharides is even more beneficial to infants than a single structure. For this reason, the milk of domestic animals has become a focal point in recent years as an alternative source of complex oligosaccharides with associated biological activity. This review will focus specifically on free oligosaccharides found in bovine and caprine milk and the biological roles associated with such structures. These dairy streams are ideal sources of oligosaccharides, given their wide availability and use in so many regularly consumed dairy products. The aim of this review was to provide an overview of research into the functional role of bovine and caprine milk oligosaccharides in host-microbial interactions in the gut and provide current knowledge related to the isolation of oligosaccharides as ingredients for incorporation in functional or medical foods.
Topics: Animals; Cattle; Gastrointestinal Microbiome; Gastrointestinal Tract; Goats; Humans; Infant; Milk; Milk, Human; Oligosaccharides; Trisaccharides
PubMed: 32089300
DOI: 10.3168/jds.2019-17645 -
The Journal of Nutrition Jul 2023Understanding how human milk impacts growth requires valid analytical methods for quantifying the composition. Lactose, the most abundant constituent in human milk and a...
BACKGROUND
Understanding how human milk impacts growth requires valid analytical methods for quantifying the composition. Lactose, the most abundant constituent in human milk and a predominant source of energy, is often assessed using methods borrowed from the bovine dairy industry. However, the carbohydrate matrices of bovine and human milk are quite different, especially as they relate to human milk oligosaccharides (HMOs), each with a terminal lactose unit that may influence analytical methods.
OBJECTIVES
Our goals were to determine the extent to which HMOs influence common analytical methods for measuring carbohydrates in human milk and to compare common methods for measuring lactose.
METHODS
Two sets of experiments were performed. In the first set, native and HMO-spiked human milk samples (n = 16 each) were assessed and compared using 4 methods: AOAC 2006.06 (based on the Megazyme enzymatic assay), BioVision enzymatic assay, ultraperformance LC with MS, and infrared analysis. In the second set, human milk samples (n = 20) were assessed using 2 methods approved for measuring lactose in bovine milk: AOAC 984.22 that uses high-performance LC and refractive index detection and AOAC 2006.06 prepared using both volume and weighted dilutions.
RESULTS
Native and HMO-spiked samples were not significantly different in lactose using AOAC 2006.06 and ultraperformance LC with MS but were significantly different using BioVision (mean difference = 0.2 g/dL; 95% CI: 0.1, 0.4; P = 0.005). Total carbohydrate measurements assessed using infrared were also higher after HMO spiking (mean difference = 0.4 g/dL; 95% CI: 0.3, 0.6; P < 0.001). Only AOAC methods 984.22 and 2006.06 for measuring lactose were very highly correlated (r > 0.90, P < 0.001).
CONCLUSIONS
AOAC methods 984.22 and 2006.06 are comparable for measuring lactose in human milk and are not influenced by HMOs. HMOs influence other enzymatic methods as well as infrared analysis, which leads to an overestimate of energy values. J Nutr 2023;x:xx.
Topics: Humans; Milk, Human; Lactose; Oligosaccharides; Dietary Carbohydrates
PubMed: 37149285
DOI: 10.1016/j.tjnut.2023.05.004 -
The Journal of Nutrition Aug 2019Proteins in human milk are essential and known to support the growth, development, protection, and health of the newborn. These proteins are highly modified by glycans...
BACKGROUND
Proteins in human milk are essential and known to support the growth, development, protection, and health of the newborn. These proteins are highly modified by glycans that are currently being recognized as vital to protein structure, stability, function, and health of the intestinal mucosa. Although milk proteins have been studied, the quantitative changes in milk proteins and their respective site-specific glycosylation are unknown.
OBJECTIVE
This study expanded the analytical tools for milk proteins and their site-specific glycosylation and applied these tools to a large cohort to determine changes in individual protein concentrations and their site-specific N-glycosylation across lactation.
DESIGN
A tandem mass spectrometry method was applied to 231 breast-milk samples from 33 mothers in Davis, California, obtained during 7 different periods of lactation. Dynamic changes in the absolute abundances of milk proteins, as well as variation in site-specific N-glycosylation of individual proteins, were quantified.
RESULTS
α-Lactalbumin, β-casein, k-casein, and α-antitrypsin were significantly increased from colostrum to transitional milk (4.37 ± 1.33 g/L to 6.41 ± 0.72 g/L, 2.25 ± 0.86 g/L to 2.59 ± 0.78 g/L, 1.33 ± 0.44 g/L to 1.60 ± 0.39 g/L, and 0.09 ± 0.10 g/L to 0.11 ± 0.04 g/L, respectively; P < 0.002). α-Lactalbumin (37%), β-casein (9%), and lysozyme (159%) were higher in mature milk than in colostrum. Glycans exhibited different behavior. Fucosylated glycans of lactoferrin and high-mannose, undecorated, fucosylated, sialylated, and combined fucosylated + sialylated glycans of secretory immunoglobulin A increased during lactation even when the concentrations of the parent proteins decreased.
CONCLUSIONS
Proteins in healthy mothers vary dynamically through lactation to support the development of infants. Individual milk proteins carried unique glycan modifications that varied systematically in structure even with site specificity. The role of glycosylation in human milk proteins will be important in understanding the functional components of human milk. This trial was registered at clinicaltrials.gov as NCT01817127.
Topics: Cohort Studies; Colostrum; Female; Glycosylation; Humans; Lactation; Milk Proteins; Milk, Human; Pregnancy; Tandem Mass Spectrometry
PubMed: 31098625
DOI: 10.1093/jn/nxz086 -
Glycobiology Sep 2020Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk...
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 >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.
Topics: Humans; Mass Spectrometry; Milk, Human; Molecular Weight; Oligosaccharides
PubMed: 32248230
DOI: 10.1093/glycob/cwaa028 -
The Journal of Nutrition Jan 2005There have been considerable advances in our understanding of the diverse mixture of bioactive components in human milk that influence the immune status of infants by... (Review)
Review
There have been considerable advances in our understanding of the diverse mixture of bioactive components in human milk that influence the immune status of infants by not only providing protection but also facilitating development, tolerance, and an appropriate inflammatory response. It could be suggested that milk is the communication vehicle between the maternal immune system and the infant, a system actively directing and educating the immune, metabolic, and microflora systems within the infant, while conferring multiple means of protection from pathogens. The physiological and protective functions of many of the immune components in human milk have been deduced not from studies in infants but from what is known in other species and in vitro models. This update briefly reviews immune development in infants and focuses on current knowledge of how both the "classical" immune and the nonimmune ingredients found in mature human milk promote immune development, facilitate the development of tolerance, and regulate the inflammatory response of infants.
Topics: Anti-Bacterial Agents; Antigens, Bacterial; Fatty Acids, Unsaturated; Growth Substances; Humans; Immune Tolerance; Milk, Human
PubMed: 15623823
DOI: 10.1093/jn/135.1.1 -
Nutrients May 2024The composition of human breast milk is an ideal combination of substances necessary for the healthy development of an infant's body while protecting from pathogens and... (Review)
Review
The composition of human breast milk is an ideal combination of substances necessary for the healthy development of an infant's body while protecting from pathogens and the balanced development of the microbiota. Its composition is dynamic and changes with the age of the child, meeting their current needs. The study provides a thorough overview of human milk components, such as immunological components, growth factors, hormones, carbohydrates, lipids, minerals, and vitamins. Authors focus on capturing the most important aspects of the effects of these substances on a newborn's body, while also looking for specific connections and describing the effects on given systems. Supplementation and the use of ingredients are also discussed. The purpose of this paper is to present the current state of knowledge about the bioactive components of human milk and their impact on the growth, development, and health of the young child.
Topics: Milk, Human; Humans; Infant; Child Development; Infant, Newborn; Child Health; Infant Nutritional Physiological Phenomena; Female; Dietary Supplements; Child, Preschool; Child
PubMed: 38794725
DOI: 10.3390/nu16101487 -
The Journal of Nutrition Jun 2021Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile... (Review)
Review
Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile are poorly defined. Thus, we aimed to review the existing evidence on the associations between nongenetic maternal and infant factors and HMO composition. A systematic search was performed on PubMed and Web of Science (without a time restriction) to identify any relevant studies published. In total, 1056 results were obtained, of which 29 articles were selected to be included in this review. The range of factors investigated include lactation stage, maternal pre-pregnancy BMI (ppBMI), maternal age, parity, maternal diet, mode of delivery, infant gestational age, and infant sex. The data suggest that, beyond maternal genetics, HMO composition seems to be influenced by all these factors, but the underlining mechanisms remain speculative. The published evidence is discussed in this review, along with potential implications for infant growth and development. For example, 2'-fucosyllactose, which was reportedly increased in mothers with higher ppBMIs, was also associated with increased infant weight and height. In addition, greater levels of sialylated HMOs after preterm birth may support brain development in these infants.
Topics: Breast Feeding; Female; Humans; Infant; Infant, Newborn; Lactation; Milk, Human; Oligosaccharides; Pregnancy; Premature Birth
PubMed: 33768224
DOI: 10.1093/jn/nxab028 -
Nature Communications Nov 2018Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors...
Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.
Topics: Feces; Gastrointestinal Microbiome; Humans; Infant, Newborn; Milk, Human; Oligosaccharides; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 30479342
DOI: 10.1038/s41467-018-07476-4