Human milk contains an abundance of biologically active components that are highly likely to contribute to the short- and long-term benefits of breastfeeding. Many of these components are proteins; ...this article describes some of these proteins, such as α-lactalbumin, lactoferrin, osteopontin, and milk fat globule membrane proteins. The possibility of adding their bovine counterparts to infant formula is discussed as well as the implications for infant health and development. An important consideration when adding bioactive proteins to infant formula is that the total protein content of formula needs to be reduced, because formula-fed infants have significantly higher concentrations of serum amino acids, insulin, and blood urea nitrogen than do breastfed infants. When reducing the protein content of formula, the amino acid composition of the formula protein becomes important because serum concentrations of the essential amino acids should not be lower than those in breastfed infants. Both the supply of essential amino acids and the bioactivities of milk proteins are dependent on their digestibility: some proteins act only in intact form, others act in the form of larger or small peptides formed during digestion, and some are completely digested and serve as a source of amino acids. The purity of the proteins or protein fractions, potential contaminants of the proteins (such as lipopolysaccharide), as well as the degree of heat processing used during their isolation also need to be considered. It is likely that there will be more bioactive components added to infant formulas in the near future, but guidelines on how to assess their bioactivities in vitro, in animal models, and in clinical studies need to be established. The extent of testing needed is likely going to depend on the degree of complexity of the components and their bioequivalence with the human compounds whose effects they are intended to mimic.
Bioactive proteins in breast milk Lönnerdal, Bo
Journal of paediatrics and child health,
March 2013, Letnik:
49, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Human milk contains many proteins that have been shown to be bioactive, but it is still not known whether these activities are exerted in breast‐fed infants. These bioactivities include enzyme ...activities, enhancement of nutrient absorption, growth stimulation, modulation of the immune system and defence against pathogens. The antimicrobial activities are very diverse, ranging from stimulation of beneficial microorganisms (i.e. prebiotic effects), killing or inhibition of growth of pathogens, to mechanisms preventing attachment or invasion of harmful microorganisms. Among the bioactive proteins are lactoferrin, lysozyme, secretory immunoglobulin A, haptocorrin, lactoperoxidase, α‐lactalbumin, bile salt stimulated lipase, β‐ and κ‐casein, and tumour growth factor β. Human milk proteins may be largely resistant against digestion in the gastrointestinal tract, be partially digested into bioactive peptides, or be more or less completely digested and utilised as a source of amino acids. These events can be studied using an in vitro digestion model, which is useful for predicting results in human infants. Some bovine milk proteins, for example, lactoferrin and tumour growth factor β, may also resist proteolysis and be capable of exerting bioactivities similar to those of human milk proteins.
The provision of iron via supplementation or the fortification of foods has been shown to be effective in preventing and treating iron deficiency and iron deficiency anemia in infants and young ...children. However, iron is a pro-oxidative element and can have negative effects on biological systems even at moderate amounts. An increasing number of studies have reported adverse effects of iron that was given to infants and young-children populations who initially were iron replete. These effects include decreased growth (both linear growth and weight), increased illness (usually diarrhea), interactions with other trace elements such as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased inflammatory markers, and impaired cognitive and motor development. If these results can be confirmed by larger and well-controlled studies, it may have considerable programmatic implications (e.g., the necessity to screen for iron status before interventions to exclude iron-replete individuals). A lack of understanding of the mechanisms underlying these adverse outcomes limits our ability to modify present supplementation and fortification strategies. This review summarizes studies on the adverse effects of iron on various outcomes; suggests possible mechanisms that may explain these observations, which are usually made in clinical studies and intervention trials; and gives examples from animal models and in vitro studies. With a better understanding of these mechanisms, it may be possible to find novel ways of providing iron in a form that causes fewer or no adverse effects even when subjects are iron replete. However, it is apparent that our understanding is limited, and research in this area is urgently needed.
Meeting the requirement for absorbed iron is difficult for vegetarians, and their iron status often is lower than that of nonvegetarians. Beans contain ferritin in low concentrations, but it is ...possible to enhance this content by plant breeding or by inserting the gene for ferritin into plants, eg, soybeans. Because each ferritin molecule can bind to thousands of iron atoms, this may be a sustainable means to increase the iron contents of plants. Before such efforts are launched, it is important to determine whether iron in ferritin is bioavailable. This has been assessed in vitro by using human intestinal (Caco-2) cells and in vivo by using radiolabeled ferritin and whole-body counting in human subjects. Dietary factors affecting iron absorption, eg, ascorbic acid, phytate, and calcium, had limited effect on iron uptake from intact ferritin by Caco-2 cells, which suggests that ferritin-bound iron is absorbed via a mechanism different from that of nonheme iron. In an in vitro digestion system, ferritin was shown to be relatively resistant to proteolytic enzymes. Binding of ferritin to Caco-2 cells was shown to be saturable, and the kinetics for binding were characteristic of a receptor-mediated process. In human subjects, iron from purified soybean ferritin given in a meal was as well absorbed as iron from ferrous sulfate. In conclusion, iron is well absorbed from ferritin and may represent a means of biofortification of staple foods such as soybeans.
Breast milk confers many benefits to the newborn and developing infant. There is substantial support for better long-term outcomes, such as less obesity, diabetes, and cardiovascular disease, in ...breastfed compared with formula-fed infants. More short-term outcomes, such as incidence and duration of illness, nutrient status, and cognitive development during the first year of life also demonstrate benefits of breastfeeding. Several proteins in breast milk, including lactoferrin, α-lactalbumin, milk fat globule membrane proteins, and osteopontin, have been shown to have bioactivities that range from involvement in the protection against infection to the acquisition of nutrients from breast milk. In some cases, bovine counterparts of these proteins exert similar bioactivities. It is possible by dairy technology to add protein fractions highly enriched in these proteins to infant formula.
Zinc (Zn) supplementation stimulates bone growth in Zn-deficient humans and animals. A biphasic pattern of mineralization has been observed in cultured osteoblasts; an initiation phase and a ...progression phase. We used MC3T3-E1, a murine osteoblastic cell line, to elucidate the physiological role of Zn in osteoblast mineralization and cellular Zn trafficking during the mineralization event. Cells were cultured in media containing Chelex-treated fetal bovine serum and 1, 4, 10 and 20 μM Zn as ZnSO
4 for 14 days (early phase of mineralization) or 21 days (mid-to-late phase of mineralization). During the early phase of mineralization, Alizarin Red staining indicated that mineralization was increased by Zn in a dose-dependent manner. Although Zn exposure did not affect monolayer Zn concentration, metallothionein (MT) mRNA expression increased dose-dependently as assessed by real-time PCR. During the late phase of mineralization, mineralization was maximal at 1 μM Zn and monolayer Zn concentration reflected Zn exposure. The increase in MT mRNA expression during the late phase was similar to that during the early phase, but the difference in expression between culture Zn concentrations tended to be smaller. ZnT-2 mRNA expression decreased significantly with increasing zinc concentrations in the culture medium during the early phase, but increased significantly during the late phase. Osteocalcin mRNA levels were positively correlated to Zn exposure at both time points. Taken together, we propose that Zn may play an important role in osteoblast mineralization through Zn trafficking involving Zn storage proteins and Zn transporters.
The milk fat globule membrane (MFGM) contains proteins which have been implicated in a variety of health benefits. Milk fat globule membrane proteins were isolated from human milk during a 12 month ...lactation period and subjected to in-solution digestion and liquid chromatography tandem mass spectrometry analysis. Data were pooled, and our results showed that 191 proteins were identified. Relative quantification of the identified MFGM proteins during the course of lactation was performed by label free spectral counting and differentiation expression analysis, which showed some proteins decreasing during the course of lactation whereas some increased or remained at a relatively constant level. The human MFGM proteins are distributed between intracellular, extracellular, and membrane-associated proteins, and they are mainly involved in cell communication and signal transduction, immune function, metabolism and energy production. This study provides more insights into the dynamic composition of human MFGM proteins, which in turn will enhance our understanding of the physiological significance of MFGM proteins.
Human milk is a rich source of bioactive proteins that support the early growth and development of the newborn. Although the major components of the protein fraction in human milk have been studied, ...the expression and relative abundance of minor components have received limited attention. We examined the expression of low-abundance proteins in the whey fraction of human milk and their dynamic changes over a twelve-month lactation period. The low-abundance proteins were enriched by ProteoMiner beads, and protein identification was performed by liquid chromatography tandem mass spectrometry. One hundred and fifteen proteins were identified, thirty-eight of which have not been previously reported in human colostrum or milk. We also for the first time described differences in protein patterns among the low-abundance proteins during lactation. These results enhance our knowledge about the complexity of the human milk proteome, which constitutes part of the advantages to the breast-fed infant.
Healthy, term, breastfed infants usually have adequate iron stores that, together with the small amount of iron that is contributed by breast milk, make them iron sufficient until ≥6 mo of age. The ...appropriate concentration of iron in infant formula to achieve iron sufficiency is more controversial. Infants who are fed formula with varying concentrations of iron generally achieve sufficiency with iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of breastfed infants at 6 mo of age). Regardless of the feeding choice, infants' capacity to regulate iron homeostasis is important but less well understood than the regulation of iron absorption in adults, which is inverse to iron status and strongly upregulated or downregulated. Infants who were given daily iron drops compared with a placebo from 4 to 6 mo of age had similar increases in hemoglobin concentrations. In addition, isotope studies have shown no difference in iron absorption between infants with high or low hemoglobin concentrations at 6 mo of age. Together, these findings suggest a lack of homeostatic regulation of iron homeostasis in young infants. However, at 9 mo of age, homeostatic regulatory capacity has developed although, to our knowledge, its extent is not known. Studies in suckling rat pups showed similar results with no capacity to regulate iron homeostasis at 10 d of age when fully nursing, but such capacity occurred at 20 d of age when pups were partially weaned. The major iron transporters in the small intestine divalent metal-ion transporter 1 (DMT1) and ferroportin were not affected by pup iron status at 10 d of age but were strongly affected by iron status at 20 d of age. Thus, mechanisms that regulate iron homeostasis are developed at the time of weaning. Overall, studies in human infants and experimental animals suggest that iron homeostasis is absent or limited early in infancy largely because of a lack of regulation of the iron transporters DMT1 and ferroportin.
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