Components Of Human Breast Milk Research Articles

Dynamic change, influencing factors, and clinical impact of cellular components in human breast milk.

Numerous cellular components have been well demonstrated in human breast milk. However, little is known about their dynamic change, influencing factors, and potential clinical impacts on infants. Sixty and forty-five healthy mother-infant pairs were enrolled in the colostrum group and mature milk group, respectively. Participants' demographic and clinical information were collected by questionnaires, and the infants were followed up until 6 months after birth through telephone interview. Colostrum and mature milk were collected, and the percentage of various cell components were determined by flow cytometric analysis. The results showed that, the total cell numbers, and the percentages of some stem cells, including CD34+, CD117+, CD133+, CD90+, CD105+, and CD146+ cells, were different in colostrum and mature milk. Besides, participants' characteristics had influence on the cellular components. Finally, high-CD34+ cells in colostrum, as well as the high-CD133+ cells and low-CD105+ cells in mature milk were associated with a significantly increased risk of infantile eczema within their first 3 months after birth. Our data showed a dynamic change of cellular components, identified some of their influencing factors and their potential clinical impacts on infantile eczema, which helps to better understand the cellular components in human breast milk. Some stem cell markers were dynamically changed in human colostrum and mature milk. Different cellular components were shown to be influenced by different participants' characteristics. High percentage of CD34+ cells in colostrum, as well as high percentage of CD133+ cells and low percentage of CD105+ cells in mature milk, were associated with a significantly increased risk of infantile eczema within their first 3 months after birth. To our knowledge, this is the first study on the clinical impacts of stem cells on infantile diseases, which helps to give a better understanding of human breast milk.

Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects.

Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant’s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.

Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers.

Breastfeeding is associated with long-term wellbeing including low risks of infectious diseases and non-communicable diseases such as asthma, cancer, autoimmune diseases and obesity during childhood. In recent years, important advances have been made in understanding the human breast milk (HBM) composition. Breast milk components such as, non-immune and immune cells and bioactive molecules, namely, cytokines/chemokines, lipids, hormones, and enzymes reportedly play many roles in breastfed newborns and in mothers, by diseases protection and shaping the immune system of the newborn. Bioactive components in HBM are also involved in tolerance and appropriate inflammatory response of breastfed infants if necessary. This review summarizes the current literature on the relationship between mother and her infant through breast milk with regard to disease protection. We will shed some light on the mechanisms underlying the roles of breast milk components in the maintenance of health of both child and mother.

Analysis of Polybrominated Diphenyl Ethers and Lipid Composition in Human Breast Milk and Their Correlation with Infant Neurodevelopment.

Breastfeeding is recommended over formula feeding, but human breast milk (HBM) composition varies and can be affected by food additives. Whether flame-retardant polybrominated diphenyl ethers (PBDEs) found in HBM interact with lipid components of HBM to impede infant neurodevelopment is a critical public health issue. Using lipidomic analysis, we examined the association of PBDEs in HBM and HBM lipid components with infant neurodevelopment. HBM samples (n = 100) were collected at the beginning stage of breastfeeding and analyzed for 30 PBDE congeners as well as a group of lipid components by using high-resolution gas chromatography, mass spectrometry, and liquid chromatography time-of-flight mass spectrometry. Infants were examined at 8 to 12 months of age by using the Bayley-III to assess neurodevelopment. A total of seven PBDEs, 35 lipids, and 27 fatty acids in HBM showed significant associations with Bayley-III scores. Multivariate analysis confirmed that these candidate PBDEs and lipid components were significant predictors of infant neurodevelopment. Eicosapentaenoic acid and docosapentaenoic acid in HBM showed no association with infant neurodevelopment in the general Taiwanese population. While certain PBDEs may play a role, our findings indicate that the lipid components of HBM are directly important for infant neurodevelopment.

Cultures of Fermentation

Cultures of Fermentation

Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model.

Breastfeeding has been associated with long lasting health benefits. Nutrients and bioactive components of human breast milk promote cell growth, immune development, and shield the infant gut from insults and microbial threats. The molecular and cellular events involved in these processes are ill defined. We have established human pediatric enteroids and interrogated maternal milk’s impact on epithelial cell maturation and function in comparison with commercial infant formula. Colostrum applied apically to pediatric enteroid monolayers reduced ion permeability, stimulated epithelial cell differentiation, and enhanced tight junction function by upregulating occludin. Breast milk heightened the production of antimicrobial peptide α-defensin 5 by goblet and Paneth cells, and modulated cytokine production, which abolished apical release of pro-inflammatory GM-CSF. These attributes were not found in commercial infant formula. Epithelial cells exposed to breast milk elevated apical and intracellular pIgR and enabled maternal IgA translocation. Proteomic data revealed a breast milk-induced molecular pattern associated with tissue remodeling and homeostasis. Using a novel ex vivo pediatric enteroid model, we have identified distinct cellular and molecular events involved in human milk-mediated improvement of human intestinal physiology and immunity.

Human breast milk-based nutritherapy: A blueprint for pediatric healthcare.

Human Breast Milk (HBM) is a storehouse of micronutrients, macronutrients, immune factors, microbiota and numerous other bioactive macromolecules. Fulfilment of optimum nutritional requirements of more than 240 million malnourished infants worldwide is possible via adequate amount (570–900 mL/d) of breast milk administration to infants in first few years of life. Technological advancements enable study of multiple components of HBM like stem cells, bioactive proteins, micro RNAs, immunoglobulins and epithelial cells to understand their role in enhancement of nutritional value of HBM. Furthermore, immunological and protective functions of HBM against various illnesses like diabetes, anemia, respiratory and cardiovascular abnormalities, otitis media and gastrointestinal diseases prove superiority of HBM over artificial milk. Presence of major macronutrients like fatty acids, sphingomyelins, proteins, peptides, lactoferrin, lactalbumins, lysozymes, mucins, growth factors, oligosaccharides and cytokines increase nutritive value of HBM. In the future, HBM can serve as a carrier for delivery of drugs, vaccines and genes to infants and offer novel therapeutic applications to stimulate effective health, growth and development of infants. The review article highlights multimodal nutritional benefits of HBM, provides insight into preclinical and clinical studies of HBM-based therapeutics and encourages further research on HBM therapy to suffice nutritional needs of infants.

Breast Milk: A Source of Functional Compounds with Potential Application in Nutrition and Therapy.

Breast milk is an unbeatable food that covers all the nutritional requirements of an infant in its different stages of growth up to six months after birth. In addition, breastfeeding benefits both maternal and child health. Increasing knowledge has been acquired regarding the composition of breast milk. Epidemiological studies and epigenetics allow us to understand the possible lifelong effects of breastfeeding. In this review we have compiled some of the components with clear functional activity that are present in human milk and the processes through which they promote infant development and maturation as well as modulate immunity. Milk fat globule membrane, proteins, oligosaccharides, growth factors, milk exosomes, or microorganisms are functional components to use in infant formulas, any other food products, nutritional supplements, nutraceuticals, or even for the development of new clinical therapies. The clinical evaluation of these compounds and their commercial exploitation are limited by the difficulty of isolating and producing them on an adequate scale. In this work we focus on the compounds produced using milk components from other species such as bovine, transgenic cattle capable of expressing components of human breast milk or microbial culture engineering.

Immunomodulatory Effects of Human Colostrum and Milk.

The immune system is not fully developed in human neonates and infants; breastfeeding is important in this stage as the bioactive components of human breast milk are known to have anti-microbial, anti-inflammatory, and immunomodulatory effects, and can therefore contribute to an infant's immunity against allergies, asthma, autoimmune diseases, and inflammatory bowel disease. Herein, the positive effect on the immune system by human colostrum and milk are reviewed.

In Love with Shaping You-Influential Factors on the Breast Milk Content of Human Milk Oligosaccharides and Their Decisive Roles for Neonatal Development.

Human milk oligosaccharides (HMOs) are structurally versatile sugar molecules constituting the third major group of soluble components in human breast milk. Based on the disaccharide lactose, the mammary glands of future and lactating mothers produce a few hundreds of different HMOs implicating that their overall anabolism utilizes rather high amounts of energy. At first sight, it therefore seems contradictory that these sugars are indigestible for infants raising the question of why such an energy-intensive molecular class evolved. However, in-depth analysis of their molecular modes of action reveals that Mother Nature created HMOs for neonatal development, protection and promotion of health. This is not solely facilitated by HMOs in their indigestible form but also by catabolites that are generated by microbial metabolism in the neonatal gut additionally qualifying HMOs as natural prebiotics. This narrative review elucidates factors influencing the HMO composition as well as physiological roles of HMOs on their way through the infant body and within the gut, where a major portion of HMOs faces microbial catabolism. Concurrently, this work summarizes in vitro, preclinical and observational as well as interventional clinical studies that analyzed potential health effects that have been demonstrated by or were related to either human milk-derived or synthetic HMOs or HMO fractions.

More than Nutrition: Therapeutic Potential of Breast Milk-Derived Exosomes in Cancer.

Human breast milk (HBM) is an irreplaceable source of nutrition for early infant growth and development. Breast-fed children are known to have a low prevalence and reduced risk of various diseases, such as necrotizing enterocolitis, gastroenteritis, acute lymphocytic leukemia, and acute myeloid leukemia. In recent years, HBM has been found to contain a microbiome, extracellular vesicles or exosomes, and microRNAs, as well as nutritional components and non-nutritional proteins, including immunoregulatory proteins, hormones, and growth factors. Especially, the milk-derived exosomes exert various physiological and therapeutic function in cell proliferation, inflammation, immunomodulation, and cancer, which are mainly attributed to their cargo molecules such as proteins and microRNAs. The exosomal miRNAs are protected from enzymatic digestion and acidic conditions, and play a critical role in immune regulation and cancer. In addition, the milk-derived exosomes are developed as drug carriers for delivering small molecules and siRNA to tumor sites. In this review, we examined the various components of HBM and their therapeutic potential, in particular of exosomes and microRNAs, towards cancer.

High-Titer De Novo Biosynthesis of the Predominant Human Milk Oligosaccharide 2'-Fucosyllactose from Sucrose in Escherichia coli.

Human milk oligosaccharides (HMOs) are unique components of human breast milk. Their large-scale production by fermentation allows infant formulas to be fortified with HMOs, but current fermentation processes require lactose as a starting material, increasing the costs, bioburden, and environmental impact of manufacturing. Here we report the development of an Escherichia coli strain that produces 2'-fucosyllactose (2'-FL), the most abundant HMO, de novo using sucrose as the sole carbon source. Strain engineering required the expression of a novel glucose-accepting galactosyltransferase, overexpression of the de novo UDP-d-galactose and GDP-l-fucose pathways, the engineering of an intracellular pool of free glucose, and overexpression of a suitable α(1,2)-fucosyltransferase. The export of 2'-FL was facilitated using a sugar efflux transporter. The final production strain achieved 2'-FL yields exceeding 60 g/L after fermentation for 84 h. This efficient strategy facilitates the lactose-independent production of HMOs by fermentation, which will improve product quality and reduce the costs of manufacturing.

Components of human breast milk: from macronutrient to microbiome and microRNA.

Human breast milk (HBM) is essential for the infant’s growth and development right after birth and is an irreplaceable source of nutrition for early human survival. Various infant formulas have many similarities to HBM in many components, but there is no perfect substitute for HBM. Recently, various breast milk components and their roles have been studied according to the development of various analysis techniques. As is already well known, HBM contains about 87%–88% water, and 124- g/L solid components as macronutrients, including about 7% (60–70 g/L) carbohydrates, 1% (8–10 g/L) protein, and 3.8% (35–40 g/L) fat. The composition may vary depending on the environmental factors, including maternal diet. Colostrum is low in fat but high in protein and relatively rich in immune-protective components. Although HBM contains enough vitamins to ensure normal growth of the infant, vitamins D and K may be insufficient, and the infant may require their supplementation. Growth factors in HBM also serve as various bioactive proteins and peptides on the intestinal tract, vasculature, nervous system, and endocrine system. In the past, HBM of a healthy mother was thought to be sterile. However, several subsequent studies have confirmed the presence of rich and diverse microbial communities in HBM. Some studies suggested that the genera Staphylococcus and Streptococcus may be universally predominant in HBM, but the origin of microbiota still remains controversial. Lastly, milk is the one of most abundant body fluid of microRNAs, which are known to play a role in various functions, such as immunoprotection and developmental programming, through delivering from HBM and absorption by intestinal epithelial cells. In conclusion, HBM is the most important source of nutrition for infants and includes microbiomes and miRNAs for growth, development, and immunity.

The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review.

Necrotizing enterocolitis, a potentially fatal intestinal inflammatory disorder affecting primarily premature infants, is a significant cause of morbidity and mortality in neonates. While the etiology of the disease is, as yet, unknown, a number of risk factors for the development of necrotizing enterocolitis have been identified. One such risk factor, formula feeding, has been shown to contribute to both increased incidence and severity of the disease. The protective influences afforded by breastfeeding are likely attributable to the unique composition of human milk, an extremely potent, biologically active fluid. This review brings together knowledge on the pathogenesis of necrotizing enterocolitis and current thinking on the instrumental role of one of the more prominent classes of bioactive components in human breast milk, glycosaminoglycans.

The renaissance of yeasts as microbial factories in the modern age of biomanufacturing.

Yeasts are essential for many processes, including the production of some of our most beloved foods and beverages. Less is known to the public about the far-reaching impacts of yeasts on other products such as biofuels, pharmaceuticals, and industrial products. By leveraging and combining newly discovered yeast genetic diversity with now affordable and efficient genetic engineering and synthetic biology tools, academic and industrial yeast labs have designed yeast cell factories for a wide range of novel applications such as the production of medicines, components of human breast milk, heme for meat substitutes, bioplastics, and other biomaterials. This review covers the newest technologies developed for yeast research including synthetic biology and their use in the engineering of yeast cell factories for emerging applications.

2586. Human Breast Milk Inhibits the Replication of Parechovirus-A3

BackgroundParechovirus-A3 (PeV-A3) is an emerging pathogen causing sepsis and meningoencephalitis in neonates and young infants. We previously reported that maternal antibodies against PeV-A3 are important to protect neonates and young infants from the infection. Recent studies showed that (1) breastfeeding had a protective effect against enterovirus, which is closely-related virus to PeV-A, and (2) human breast milk (HBM) neutralized enterovirus in vitro. Currently, no report is available related to the antiviral effect of HBM against PeV-A3.MethodsHBM (colostrum, 3–5 days after childbirth; mature milk, 1 month after childbirth) and serum (within ± 1 week of child’s birthday) samples were obtained from mothers at obstetrics clinic in Niigata, Japan. Neutralizing antibody titers (NATs) against PeV-A3 were measured using the Vero cells.ResultsThe anti-PeV-A3 NATs of colostrum (n = 32) ranged from 1:8 to 1:2048, those ≥1:32 was 59% (19/32). Whereas, the anti-PeV-A3 NATs of mature milk ranged from 1:8 to 1:96. and those ≥1:32 was 20% (2/20) (P < 0.001). The median NATs anti-PeV-A3 was higher in colostrum (1:32) compared with mature milk (1:8) (P < 0.001). There was a strong positive correlation between the NATs of colostrum and serum (r = 0.604, P < 0.001, Figure).ConclusionThis study showed that HBM had high NATs against PeV-A3, which was correlated with serum NATs. Further studies are necessary to investigate which components of HBM has antiviral effects against PeV-A3. Disclosures All authors: No reported disclosures.

Human Milk Oligosaccharide, Phospholipid, and Ganglioside Concentrations in Breast Milk from United Arab Emirates Mothers: Results from the MISC Cohort.

Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5–15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers’ transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.

Analysis of Fucosylated Human Milk Trisaccharides in Biotechnological Context Using Genetically Encoded Biosensors.

Human milk oligosaccharides (HMOs) are complex carbohydrate components of human breast milk that exhibit plentiful benefits on infant health. However, optimization of their biotechnological synthesis is limited by the relatively low throughput of detection and quantification of monosaccharide and linkages. Conventional techniques of glycan analysis include chromatographic/mass-spectrometric methods with throughput on the order of hundreds of samples per day without automation. We demonstrate here, a genetically encoded bacterial biosensor for the high-throughput, linkage-specific detection and quantification of the fucosylated HMO structures, 2'-fucosyllactose and 3-fucosyllactose, which we achieved via heterologous expression of fucosidases. As the presence of lactose in milk or in biotechnological processes could lead to false positives, we also demonstrate the reduction of signal from lactose using different strategies. Due to the high throughput of this technique, many reaction conditions or bioreactor parameters could be assayed in parallel in a matter of hours, allowing for the optimization of HMO manufacturing.

Chemistry of Human Breast Milk-A Comprehensive Review of the Composition and Role of Milk Metabolites in Child Development.

Early nutrition has an enormous influence on a child's physiological function, immune system maturation, and cognitive development. Human breast milk (HBM) is recognized as the gold standard for human infant nutrition. According to a WHO report, breastfeeding is considered as an unequaled way of providing ideal food to the infant, which is required for his healthy growth and development. HBM contains various macronutrients (carbohydrates, proteins, lipids, and vitamins) as well as numerous bioactive compounds and interactive elements (growth factors, hormones, cytokines, chemokines, and antimicrobial compounds. The aim of this review is to summarize and discuss the current knowledge about metabolites, which are the least understood components of HBM, and their potential role in infant development. We focus on small metabolites (<1500 Da) and characterize the chemical structure and biological function of polar metabolites such as human milk oligosaccharides, nonprotein molecules containing nitrogen (creatine, amino acids, nucleotides, polyamines), and nonpolar lipids. We believe that this manuscript will provide a comprehensive insight into a HBM metabolite composition, chemical structure, and their role in a child's early life nutrition.

Lactational changes in the human milk oligosaccharide concentration in Chinese and Malaysian mothers' milk

Oligosaccharides are important components of human breast milk with bioefficacy as prebiotics, anti-infectives and immune system modulators, and as a source of sialic acid for neural function and development. Recently, human milk oligosaccharides have been synthesised artificially as ingredients for commercial use, in infant formulae. However, incorporation of human milk oligosaccharides into paediatric foods requires a prior understanding of variations in the levels of oligosaccharides in human breastmilk – between individuals, populations, and lactational stages. In this study, seven acidic [3′-sialyl lactose, 6′-sialyl lactose, 6′-sialyl lactosamine, 3′-sialyl-3-fucosyllactose, disialyl lactose, LS-tetrasaccharide a/b and LS-tetrasaccharide c] and five neutral [lacto-N-neotetraose, lacto-N-tetraose, lacto-N-fucopentaose (total), 2′-fucosyllactose and 3-fucosyllactose] oligosaccharides from the breast milk of Chinese and Malaysian mothers were quantified using high performance liquid chromatography-mass spectrometry, with an internal standard, in multiple reaction monitoring mode. In addition, the changes in the HMOs at an individual level were monitored across lactation.