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International Journal of Molecular... Aug 2021Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These... (Review)
Review
Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. However, HM hormone studies are sparse and heterogeneous in regard to the study design, sample collection, preparation and analysis methods. This review discussed the limitations of HM hormone analysis highlighting the gaps in pre-analytical and analytical stages. The methods used to quantify HM metabolic hormones (leptin, adiponectin, ghrelin, insulin, obestatin, resistin and apelin) can be classified as immunoassay, immunosensor and chromatography. Immunoassay methods (ELISA and RIA) have been predominantly used in the measurement of these HM hormones. The relative validity parameters of HM hormones analysis are often overlooked in publications, despite the complexity and differences of HM matrix when compared to that of plasma and urine. Therefore, appropriate reports of validation parameters of methodology and instrumentation are crucial for accurate measurements and therefore better understanding of the HM metabolic hormones and their influences on infant outcomes.
Topics: Biosensing Techniques; Chromatography; Female; Humans; Immunoassay; Milk, Human; Peptide Hormones
PubMed: 34445437
DOI: 10.3390/ijms22168708 -
Frontiers in Immunology 2019The postpartum period is an important window during which environmental factors can shape the life-long health of the infant. This time period often coincides with... (Review)
Review
The postpartum period is an important window during which environmental factors can shape the life-long health of the infant. This time period often coincides with substantial milk consumption either in the form of breast milk or from cow's milk sources, such as infant formulas. Although breast milk is the most beneficial source of nutrients for infants during the first 6 months after birth, its role in regulating food allergy development, through regulation of oral tolerance, is still controversial. Breast milk contains several factors that can impact mucosal immune function, including immune cells, antibodies, microbiota, oligosaccharides, cytokines, and soluble receptors. However, there is considerable variation in the assessed levels of cytokines and soluble receptors between studies and across the lactation period. Most of these cytokines and soluble receptors are absent, or only found in limited quantities, in commercial baby formulas. Differences in content of these pluripotent factors, which impact on both the mother and the neonate, could contribute to the controversy surrounding the role of breast milk regulating oral tolerance. This review highlights current knowledge about the importance of cytokines and soluble receptors in breast milk on the development of oral tolerance and tolerance-relateddisorders. Understanding the mechanisms by which such milk components might promote oral tolerance could aid in the development of improved strategies for allergy prevention.
Topics: Animals; Breast Feeding; Cytokines; Desensitization, Immunologic; Humans; Hypersensitivity; Immune Tolerance; Milk, Human; Receptors, Cytokine
PubMed: 30723472
DOI: 10.3389/fimmu.2019.00016 -
Current Opinion in Clinical Nutrition... May 2015Provide research that relates the developing intestinal microbiome, nutrition, and the subsequent host response to the development of necrotizing enterocolitis (NEC),... (Review)
Review
PURPOSE OF REVIEW
Provide research that relates the developing intestinal microbiome, nutrition, and the subsequent host response to the development of necrotizing enterocolitis (NEC), one of the most common and deadliest diseases seen in newborn infants. After nearly 50 years of little to no progress in this area, we are finally beginning to obtain evidence that is likely to lead to better understanding of both pathophysiology and prevention of the disease.
RECENT FINDINGS
We will discuss new discoveries related to the development of the microbiome from prenatal to postnatal life, as well as new findings of microbes and human milk oligosaccharides in human milk as they relate to pathogenesis of NEC. The effect of antibiotics and acid blocking agents, as they may increase the odds of development of NEC, will also be discussed.
SUMMARY
The implications of these findings are that improved understanding of the developing microbiome, the factors that affect the microbiome including nutrition such as donor milk versus baby's own mother's milk, and certain drugs, will help clinicians to adjust their current feeding and drug utilization to potentially prevent this disease.
Topics: Antacids; Anti-Bacterial Agents; Enterocolitis, Necrotizing; Gastrointestinal Microbiome; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Milk, Human
PubMed: 25807349
DOI: 10.1097/MCO.0000000000000169 -
Amino Acids Mar 2022Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in...
BACKGROUND
Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in human milk is still poorly characterized with respect to its correlation to maternal serum levels and its physiological significance for the infant. Studies addressing the relation of human milk FAA to the infants' intestinal microbiota are still missing.
METHODS
As part of a pilot study, maternal serum and breast milk FAA concentrations as well as infant intestinal microbiota (16S rRNA) were determined 2 months after birth. The study cohort consisted of 41 healthy mothers and their term delivered, healthy infants with normal birthweight. The relationship between maternal serum and milk FAA was determined by correlation analyses. Associations between (highly correlated) milk FAA and infant intestinal beta diversity were tested using PERMANOVA, LefSe and multivariate regression models adjusted for common confounders.
RESULTS
Seven breast milk FAA correlated significantly with serum concentrations. One of these, threonine showed a negative association with abundance of members of the class Gammaproteobacteria (Radj = 17.1%, p = 0.006; β= - 0.441). In addition, on the level of families and genera, threonine explained 23.2% of variation of the relative abundance of Enterobacteriaceae (Radj; p = 0.001; β = - 0.504) and 11.1% of variability in the abundance of Escherichia/Shigella (Radj, p = 0.025; β = - 0.368), when adjusted for confounders.
CONCLUSION
Our study is the first to suggest potential interactions between breast milk FAA and infant gut microbiota composition during early lactation. The results might be indicative of a potential protective role of threonine against members of the Enterobacteriaceae family in breast-fed infants. Still, results are based on correlation analyses and larger cohorts are needed to support the findings and elucidate possible underlying mechanisms to assess the complex interplay between breast milk FAA and infant intestinal microbiota in detail.
Topics: Female; Gastrointestinal Microbiome; Humans; Infant; Milk, Human; Pilot Projects; RNA, Ribosomal, 16S; Threonine
PubMed: 34477981
DOI: 10.1007/s00726-021-03057-w -
Advances in Nutrition (Bethesda, Md.) Jan 2023When there is an inadequate supply of mother's milk, pasteurized donor human milk is preferred over formula to supplement feeds for preterm infants. Although providing... (Review)
Review
When there is an inadequate supply of mother's milk, pasteurized donor human milk is preferred over formula to supplement feeds for preterm infants. Although providing donor milk helps to improve feeding tolerance and reduce necrotizing enterocolitis, changes to its composition and reductions in bioactivity during processing, are thought to contribute to the slower growth often exhibited by these infants. To improve the clinical outcomes of recipient infants by maximizing the quality of donor milk, research is currently investigating strategies to optimize all aspects of processing, including pooling, pasteurization, and freezing; however, reviews of this literature typically only summarize the impact of a processing technique on composition or bioactivity. Reviews of published research investigating the impact of donor milk processing on infant digestion/absorption are lacking and thus, was the objective for this systematic scoping review, Open Science Framework (https://doi.org/10.17605/OSF.IO/PJTMW). Databases were searched for primary research studies evaluating donor milk processing for pathogen inactivation or other rationale and subsequent effect on infant digestion/absorption. Non-human milk studies or those assessing other outcomes were excluded. Overall, 24 articles from 12,985 records screened were included. Most studied thermal methods to inactivate pathogens, predominantly Holder pasteurization (HoP) (62.5°C, 30 min) and high-temperature short-time. Heating consistently decreased lipolysis and increased proteolysis of lactoferrin and caseins; however, protein hydrolysis was unaffected from in vitro studies. The abundance and diversity of released peptides remain unclear and should be further explored. Greater investigation into less-harsh methods for pasteurization, such as high-pressure processing, is warranted. Only 1 study assessed the impact of this technique and found minimal impact on digestion outcomes compared with HoP. Fat homogenization appeared to positively impact fat digestion (n = 3 studies), and only 1 eligible study investigated freeze-thawing. Identified knowledge gaps regarding optimal methods of processing should be further explored to improve the quality and nutrition of donor milk.
Topics: Infant, Newborn; Infant; Humans; Infant, Premature; Infant Nutritional Physiological Phenomena; Milk, Human; Nutritional Status; Digestion
PubMed: 36811588
DOI: 10.1016/j.advnut.2022.11.004 -
The Journal of Nutrition Apr 2021Human milk is the most genuine form of personalized nutrition, whereby its nutritional and bioactive constituents support the changing needs of the growing infant.... (Observational Study)
Observational Study
BACKGROUND
Human milk is the most genuine form of personalized nutrition, whereby its nutritional and bioactive constituents support the changing needs of the growing infant. Personalized proteome profiling strategies may provide insights into maternal-infant relationships. Proteins and endogenous peptides in human milk play an important role as nutrients for growth and have distinct functionality such as immune defense. Comprehensive monitoring of all of the human milk proteinaceous components, including endogenous peptides, is required to fully understand the changing role of the human milk proteome throughout lactation.
OBJECTIVE
We aimed to investigate the personalized nature of the human milk proteome and peptidome for individual mother-infant dyads.
METHODS
Two individual healthy milk donors, aged 29 and 32 y and both of a normal BMI, were longitudinally observed over weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16 postpartum. Milk collection was standardized. Comprehensive variations in the human milk proteinaceous components were assessed using quantitative LC-MS/MS methods.
RESULTS
We longitudinally profiled the concentrations of >1300 milk proteins and 2000 endogenous milk peptides spanning 16 wk of lactation for 2 individual donors. We observed many gradual and alike changes in both donors related to temporal effects, for instance early lactation was marked by high concentrations of proteins and peptides involved in lactose synthesis and immune development. Uniquely, in 1 of the 2 donors, we observed a substantial anomaly in the milk composition, exclusively at week 6, likely indicating a response to inflammation and/or infection.
CONCLUSIONS
Here, we provide a resource for characterizing the lactational changes in the human milk proteome, encompassing thousands of proteins and endogenous peptides. Further, we demonstrate the feasibility and benefit of personalized profiling to monitor the influence of milk on the development of the newborn, as well as the health status of each individual mother-infant pair.
Topics: Adult; Chromatography, Liquid; Digestive System Physiological Phenomena; Female; Humans; Immunoglobulins; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lactation; Longitudinal Studies; Milk Proteins; Milk, Human; Peptides; Polysaccharides; Postpartum Period; Precision Medicine; Protein Array Analysis; Proteome; Tandem Mass Spectrometry
PubMed: 33693758
DOI: 10.1093/jn/nxaa445 -
Advances in Nutrition (Bethesda, Md.) Apr 2024Cannabis use has increased sharply in the last 20 y among adults, including reproductive-aged women. Its recent widespread legalization is associated with a decrease in... (Review)
Review
Cannabis use has increased sharply in the last 20 y among adults, including reproductive-aged women. Its recent widespread legalization is associated with a decrease in risk perception of cannabis use during breastfeeding. However, the effect of cannabis use (if any) on milk production and milk composition is not known. This narrative review summarizes current knowledge related to maternal cannabis use during breastfeeding and provides an overview of possible pathways whereby cannabis might affect milk composition and production. Several studies have demonstrated that cannabinoids and their metabolites are detectable in human milk produced by mothers who use cannabis. Due to their physicochemical properties, cannabinoids are stored in adipose tissue, can easily reach the mammary gland, and can be secreted in milk. Moreover, cannabinoid receptors are present in adipocytes and mammary epithelial cells. The activation of these receptors directly modulates fatty acid metabolism, potentially causing changes in milk fatty acid profiles. Additionally, the endocannabinoid system is intimately connected to the endocrine system. As such, it is probable that interactions of exogenous cannabinoids with the endocannabinoid system might modify release of critical hormones (e.g., prolactin and dopamine) that regulate milk production and secretion. Nonetheless, few studies have investigated effects of cannabis use (including on milk production and composition) in lactating women. Additional research utilizing robust methodologies are needed to elucidate whether and how cannabis use affects human milk production and composition.
Topics: Adult; Female; Humans; Animals; Lactation; Milk, Human; Breast Feeding; Cannabis; Endocannabinoids; Milk; Cannabinoids; Fatty Acids
PubMed: 38432590
DOI: 10.1016/j.advnut.2024.100196 -
Advances in Nutrition (Bethesda, Md.) May 2011Human milk TG are a remarkable example of stereo-specific positioning of fatty acids with structures that are highly conserved and unusual. Not only does human milk... (Review)
Review
Human milk TG are a remarkable example of stereo-specific positioning of fatty acids with structures that are highly conserved and unusual. Not only does human milk contain high amounts of fat and 16:0, but ~70% of the 16:0 is esterified at the TG stereo-specifically numbered (sn)-2 position, with preferential positioning of 18:1(n-9) and 18:2(n-6) at the TG sn-1,3 positions. The milk TG structures and digestive lipases combine to enable efficient digestion and absorption of 16:0 by conserving 16:0 in sn-2 monoacylglycerols, which are absorbed, reassembled, and secreted in plasma conserving the original milk TG configuration; these studies are reviewed in this article. The reason why the mammary gland invests in enzymes to provide the infant with 20-25% milk fatty acids as 16:0 rather than selecting against 16:0 is unknown, yet likely has a purpose given the mammary gland capacity for 10:0, 12:0, and 14:0 synthesis. Recent advances in the development-, tissue-, and species-specific activity of enzymes of TG synthesis and knowledge that dietary TG structures are maintained postabsorption suggest that the purpose of the milk TG structures is more sophisticated than simply avoiding 16:0 malabsorption. The overall aim is to expand consideration of fatty acids in the infant diet from a simple view of average fatty acid compositions to the complex lipids and molecular structures in which fatty acids are provided to tissues during early life and the biology through which the unique features of human milk enable the infant to grow and thrive on a high-fat, high-saturated-fat milk diet.
Topics: Animals; Diet; Dietary Fats; Digestion; Fatty Acids; Humans; Infant; Infant Nutritional Physiological Phenomena; Mammary Glands, Human; Milk, Human; Triglycerides
PubMed: 22332059
DOI: 10.3945/an.111.000448 -
Postepy Higieny I Medycyny... Dec 2016Protein content in cow milk (with over 20 proteins, and peptides may also occur as a result of enzymatic hydrolysis) ranges from 2.5% to 4.2% and is about 1.5-2 times... (Review)
Review
Protein content in cow milk (with over 20 proteins, and peptides may also occur as a result of enzymatic hydrolysis) ranges from 2.5% to 4.2% and is about 1.5-2 times higher than in human milk. Its most important allergens are considered to be β-lactoglobulin (absent in human milk) and αs1-casein. The most similar in composition to human milk is horse and donkey milk. It contains considerably more whey proteins (35-50%) than cow milk (about 20%), and the concentration of the most allergenic casein fraction αs1 is 1.5-2.5 g/l. In comparison, the content of αs1-casein in cow milk is about 10 g/l. β-lactoglobulin present in donkey milk is a monomer, while in milk of ruminants it is a dimer. Like human milk, it contains a substantial amount of lactose (about 7%), which determines its flavour and facilitates calcium absorption. The high lysozyme content (about 1 g/l) gives it antibacterial properties (compared to trace amounts in ruminants). Camel milk is also more digestible and induces fewer allergic reactions, because it lacks β-lactoglobulin, and its β-casein has a different structure. It also contains (compared to cow milk) more antibacterial substances such as lysozyme, lactoferrin and immunoglobulins, and furthermore the number of immunoglobulins is compatible with human ones. Goat milk components have a higher degree of assimilability as compared to cow milk. Its main protein is β-casein, with total protein content depending on the αs1-casein genetic variant. Goats with the '0' variant do not synthesize this allergenic protein. Clinical and immunochemical studies indicate, however, that it cannot be a substitute for cow milk without the risk of an anaphylactic reaction.
Topics: Allergens; Animals; Cattle; Equidae; Female; Goats; Horses; Humans; Immunoglobulins; Lactose; Milk; Milk Proteins; Milk, Human; Muramidase
PubMed: 28100852
DOI: 10.5604/17322693.1227842 -
Analytical and Bioanalytical Chemistry Apr 2022We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2'-Fucosyllactose (2'FL) is an...
We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2'-Fucosyllactose (2'FL) is an HMO associated with infant growth, cognitive development, and protection from infectious diarrhea, one of the major causes of infant death worldwide. Due to genetic variation, the milk of some women (non-secretors) contains no or very little 2'FL with potential implications for infant health and development. However, there is currently no technology to analyze the presence and concentration of HMOs in human milk at the point-of-care (POC). The lack of such technology represents a major impediment to advancing human milk research and improving maternal-infant health. Towards this unmet need, we report an impedimetric assay for HMOs with an α-1,2 linkage, the most abundant of which is 2'FL. The sensor uses a lectin for affinity, specifically Ulex europaeus agglutinin I (UEA), with electrochemical readout. In spiked studies, the sensor exhibited a high degree of linearity (R = 0.991) over 0.5 to 3.0 μM with a 330-nM detection limit. The sensor performance was clinically validated using banked human milk samples and correctly identified all secretor vs. non-secretor samples. Furthermore, despite the short 35-min assay time and low sample volume (25 μL), the assay was highly correlated with HPLC measurements. This bedside human milk testing assay enables POC, "sample-to-answer" quantitative HMO measurement, and will be a valuable tool to assess milk composition.
Topics: Chromatography, High Pressure Liquid; Female; Humans; Infant; Milk, Human; Oligosaccharides; Point-of-Care Systems
PubMed: 34741182
DOI: 10.1007/s00216-021-03697-7