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Nutrients May 2024Milk bioactivity refers to the specific health effects of milk components beyond nutrition. The science of milk bioactivity involves the systematic study of these... (Review)
Review
Milk bioactivity refers to the specific health effects of milk components beyond nutrition. The science of milk bioactivity involves the systematic study of these components and their health effects, as verified by empirical data, controlled experiments, and logical arguments. Conversely, 'faith in milk bioactivity' can be defined as personal opinion, meaning, value, trust, and hope for health effects that are beyond investigation by natural, social, or human sciences. Faith can be strictly secular, but also influenced by spirituality or religion. The aim of this paper is to show that scientific knowledge is frequently supplemented with faith convictions to establish personal and public understanding of milk bioactivity. Mammalian milk is an immensely complex fluid containing myriad proteins, carbohydrates, lipids, and micronutrients with multiple functions across species, genetics, ages, environments, and cultures. Human health includes not only physical health, but also social, mental, and spiritual health, requiring widely different fields of science to prove the relevance, safety, and efficacy of milk interventions. These complex relationships between milk feeding and health outcomes prevent firm conclusions based on science and logic alone. Current beliefs in and understanding of the value of breast milk, colostrum, infant formula, or isolated milk proteins (e.g., immunoglobulins, α-lactalbumin, lactoferrin, and growth factors) show that both science and faith contribute to understand, stimulate, or restrict the use of milk bioactivity. The benefits of breastfeeding for infants are beyond doubt, but the strong beliefs in its health effects rely not only on science, and mechanisms are unclear. Likewise, fear of, or trust in, infant formula may rely on both science and faith. Knowledge from science safeguards individuals and society against 'milk bioactivity superstition'. Conversely, wisdom from faith-based convictions may protect science from unrealistic 'milk bioactivity scientism'. Honesty and transparency about the potentials and limitations of both scientific knowledge and faith convictions are important when informing individuals and society about the nutritious and bioactive qualities of milk.
Topics: Humans; Milk, Human; Infant; Infant Nutritional Physiological Phenomena; Breast Feeding; Infant Formula; Infant, Newborn; Female; Colostrum; Health Knowledge, Attitudes, Practice; Animals; Milk Proteins; Religion
PubMed: 38892610
DOI: 10.3390/nu16111676 -
Nutrients May 2024Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human...
Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human milk banks is stored frozen and pasteurized, reducing its nutritional and biological value. The purpose of this study was to determine the effect of hyperbaric storage at subzero temperatures (HS-ST) on the macronutrients and bioactive proteins in HM. As control samples, HM was stored at the same temperatures under 0.1 MPa. A Miris HM analyzer was used to determine the macronutrients and the energy value. The lactoferrin (LF), lysozyme (LYZ) and lactalbumin (LAC) content was checked using high-performance liquid chromatography, and an ELISA test was used to quantify secretory immunoglobulin A (sIgA). The results showed that the macronutrient content did not change significantly after 90 days of storage at 60 MPa/-5 °C, 78 MPa/-7 °C, 111 MPa/-10 °C or 130 MPa/-12 °C. Retention higher than 90% of LYZ, LAC, LF and sIgA was observed in the HM stored at conditions of up to 111 MPa/-10 °C. However, at 130 MPa/-12 °C, there was a reduction in LYZ and LF, by 39 and 89%, respectively. The storage of HM at subzero temperatures at 0.1 MPa did not affect the content of carbohydrates or crude and true protein. For fat and the energy value, significant decreases were observed at -5 °C after 90 days of storage.
Topics: Humans; Milk, Human; Nutritive Value; Lactoferrin; Food Storage; Muramidase; Lactalbumin; Immunoglobulin A, Secretory; Nutrients; Milk Proteins; Female
PubMed: 38794693
DOI: 10.3390/nu16101455 -
Journal of Proteomics Jun 2024This study explores the disulfide bridges present in the human milk proteome by a novel approach permitting both positional identification and relative quantification of...
This study explores the disulfide bridges present in the human milk proteome by a novel approach permitting both positional identification and relative quantification of the disulfide bridges. Human milk from six donors was subjected to trypsin digestion without reduction. The digested human milk proteins were analyzed by nanoLC-timsTOF Pro combined with data analysis using xiSEARCH. A total of 85 unique disulfide bridges were identified in 25 different human milk proteins. The total relative abundance of disulfide bridge-containing peptides constituted approximately 5% of the total amount of tryptic-peptides. Seven inter-molecular disulfide bridges were identified between either α-lactalbumin and lactotransferrin (5) or α-casein and κ-casein (2). All cysteines involved in the observed disulfide bridges of α-lactalbumin and lactotransferrin were mapped onto protein models using AlphaFold2 Multimer to estimate the length of the observed disulfide bridges. The lengths of the disulfide bridges of lactotransferrin indicate a potential for multi- or poly-merization of lactotransferrin. The high number of intramolecular lactotransferrin disulfide bridges identified, suggests that these are more heterogeneous than previously presumed. SIGNIFICANCE: Disulfide-bridges in the human milk proteome are an often overseen post-transaltional modification. Thus, mapping the disulfide-bridges, their positions and relative abundance, are valuable new knowledge needed for an improved understanding of human milk protein behaviour. Although glycosylation and phosphorylation have been described, even less information is available on the disulfide bridges and the disulfide-bridge derived protein complexes. This is important for future work in precision fermentation for recombinant production of human milk proteins, as this will highlight which disulfide-bridges are naturally occouring in human milk proteins. Further, this knowledge would be of value for the infant formula industry as it provides more information on how to humanize bovine-milk based infant formula. The novel method developed here can be broadly applied in other biological systems as the disulfid-brigdes are important for the structure and functionality of proteins.
Topics: Humans; Milk, Human; Disulfides; Proteomics; Proteome; Lactoferrin; Milk Proteins; Lactalbumin; Female
PubMed: 38723850
DOI: 10.1016/j.jprot.2024.105194 -
Journal of Nutrition and Metabolism 2024Whey, a component of milk and a useful by-product of the dairy industry's casein and cheese-making, has been used for generations to augment animal feed. It contains a... (Review)
Review
Whey, a component of milk and a useful by-product of the dairy industry's casein and cheese-making, has been used for generations to augment animal feed. It contains a range of proteins, including -lactalbumin, -lactoglobulin, bovine serum albumin, heavy and light chain immunoglobulins, lactoferrin, glycomacropeptide, and lactoperoxidase. Whey proteins exhibit great potential as biopolymers for creating bioactive delivery systems owing to their distinct health-enhancing characteristics and the presence of numerous amino acid groups within their structures. Whey has considerable factors such as antitumor, anti-inflammatory, antihypertensive, hypolipidemic, antiviral, and antibacterial properties in addition to chelating. The global market of whey protein stood at USD 5.33 billion in 2021, with a projected compound annual growth rate of 10.48% spanning the interval from 2022 to 2030. The escalating demand for whey protein is intrinsically linked to the amplifying consciousness surrounding healthy lifestyles. Notably, protein supplements are recurrently endorsed by fitness and sports establishments, thereby accentuating the focal point of customers toward whey protein. This review focuses on nutritional composition, whey bioactives, and their bioavailability with potential health benefits.
PubMed: 38633607
DOI: 10.1155/2024/8455666 -
Nutrients Apr 2024High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate... (Randomized Controlled Trial)
Randomized Controlled Trial
High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants ( = 0.019; < 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group ( < 0.001; = 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.
Topics: Humans; Infant; C-Peptide; Follow-Up Studies; GTP-Binding Proteins; Infant Formula; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lactalbumin; Weight Gain; Prospective Studies
PubMed: 38613059
DOI: 10.3390/nu16071026 -
Research in Veterinary Science Jun 2024Antimicrobial usage (AMU) could be reduced by differentiating the causative bacteria in cases of clinical mastitis (CM) as either Gram-positive or Gram-negative bacteria...
Antimicrobial usage (AMU) could be reduced by differentiating the causative bacteria in cases of clinical mastitis (CM) as either Gram-positive or Gram-negative bacteria or identifying whether the case is culture-negative (no growth, NG) mastitis. Immunoassays for biomarker analysis and a Tandem Mass Tag (TMT) proteomic investigation were employed to identify differences between samples of milk from cows with CM caused by different bacteria. A total of 94 milk samples were collected from cows diagnosed with CM across seven farms in Scotland, categorized by severity as mild (score 1), moderate (score 2), or severe (score 3). Bovine haptoglobin (Hp), milk amyloid A (MAA), C-reactive protein (CRP), lactoferrin (LF), α-lactalbumin (LA) and cathelicidin (CATHL) were significantly higher in milk from cows with CM, regardless of culture results, than in milk from healthy cows (all P-values <0.001). Milk cathelicidin (CATHL) was evaluated using a novel ELISA technique that utilises an antibody to a peptide sequence of SSEANLYRLLELD (aa49-61) common to CATHL 1-7 isoforms. A classification tree was fitted on the six biomarkers to predict Gram-positive bacteria within mastitis severity scores 1 or 2, revealing that compared to the rest of the samples, Gram-positive samples were associated with CRP < 9.5 μg/ml and LF ≥ 325 μg/ml and MAA < 16 μg/ml. Sensitivity of the tree model was 64%, the specificity was 91%, and the overall misclassification rate was 18%. The area under the ROC curve for this tree model was 0.836 (95% bootstrap confidence interval: 0.742; 0.917). TMT proteomic analysis revealed little difference between the groups in protein abundance when the three groups (Gram-positive, Gram-negative and no growth) were compared, however when each group was compared against the entirety of the remaining samples, 28 differentially abundant protein were identified including β-lactoglobulin and ribonuclease. Whilst further research is required to draw together and refine a suitable biomarker panel and diagnostic algorithm for differentiating Gram- positive/negative and NG CM, these results have highlighted a potential panel and diagnostic decision tree. Host-derived milk biomarkers offer significant potential to refine and reduce AMU and circumvent the many challenges associated with microbiological culture, both within the lab and on the farm, while providing the added benefit of reducing turnaround time from 14 to 16 h of microbiological culture to just 15 min with a lateral flow device (LFD).
Topics: Animals; Cattle; Female; Milk; Mastitis, Bovine; Biomarkers; Proteome; Milk Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Cathelicidins
PubMed: 38608347
DOI: 10.1016/j.rvsc.2024.105240 -
Journal of Extracellular Vesicles Apr 2024Human milk contains extracellular vesicles (HMEVs). Pre-clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown...
Human milk contains extracellular vesicles (HMEVs). Pre-clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density-gradient ultracentrifugation following two-step skimming, acid precipitation of caseins, and multi-step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super-resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of β-casein and lactalbumin. HMEV and some dEV fractions contain mammary gland-derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin-mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs.
Topics: Infant, Newborn; Infant; Humans; Milk, Human; Extracellular Vesicles; Body Fluids; Caseins
PubMed: 38602306
DOI: 10.1002/jev2.12422 -
Foods (Basel, Switzerland) Mar 2024A strong correlation between the occurrence of various pathological conditions and intestinal dysbiosis is supported by a range of strong evidence. Vice versa, many... (Review)
Review
A strong correlation between the occurrence of various pathological conditions and intestinal dysbiosis is supported by a range of strong evidence. Vice versa, many pathologies have been shown, in turn, to be responsible for alterations in the gut microbiota, a condition that can worsen illness outcomes and response to therapies. For these reasons, great efforts have been made, and studies are still ongoing, to elucidate the mechanisms underlying gut microbiota alterations and to search for pharmacologic or other strategies that can effectively restore the gut microbiota. In this narrative review, we examined the most significant literature on the role of some milk bioactive compounds, such as milk oligosaccharides and whey proteins, in modulating the composition of the gut microbiota and the underlying mechanisms of action, with the aim of investigating the impact of the microbiota changes mediated by these milk bioactive molecules on human health, and their potential use as therapeutics to treat or adjuvate the treatment of gut dysbiosis and associated pathologies.
PubMed: 38540897
DOI: 10.3390/foods13060907 -
Journal of Oral Biology and... 2024Alpha-lactalbumin, the protein from human and bovine milk has been found to be promising as an alternative of anticancer agent This study was aimed to investigate the...
OBJECTIVES
Alpha-lactalbumin, the protein from human and bovine milk has been found to be promising as an alternative of anticancer agent This study was aimed to investigate the effects of lactalbumin enzymatic hydrolysate (LAH) on cell proliferation, migration, and mRNA expression of () on human squamous cell carcinoma (hSCC) cell lines, .
METHODS
Tongue (HSC-4 and 7) and pharyngeal (HN-30 and 31) hSCC cell lines were treated with a two-fold dilution of LAH (0.39-100 mg/ml). Cell viability and cell proliferation were examined by MTT assay. Colony forming unit (CFU) was assessed by crystal violet blue staining. Cell migration was investigated by scratch wound healing assay. Gene expression of metastasis-associated was assessed by RT-qPCR. Statistical analyses were evaluated at value = 0.05.
RESULTS
LAH at concentration of 50 and 100 mg/ml exhibited cytotoxicity on hSCC cells. The proliferation and CFU ability of hSCC cells were significantly attenuated after LAH treatment. The mRNA expression of , , and was reduced in HN-30 and HN-31 cells while expression of and was downregulated in HSC-7 cells. Only mRNA level was reduced in HSC-4 cells. However, cell migration of all hSCC cell lines did not alter after LAH treatment.
CONCLUSION
LAH treatment exhibits inhibitory effects on hSCC cell growth, proliferation and gene expression. Thus, LAH should be the promising alternative agent to develop the prospective anti-cancer drug.
PubMed: 38495954
DOI: 10.1016/j.jobcr.2024.02.011 -
Journal of Dairy Science Mar 2024Buttermilk differs from skim milk by the presence of milk fat globule membrane (MFGM) fragments that are released during cream churning. MFGM is rich in health-promoting...
Buttermilk differs from skim milk by the presence of milk fat globule membrane (MFGM) fragments that are released during cream churning. MFGM is rich in health-promoting components, such as phospholipids and membrane proteins, but these compounds have a negative impact on buttermilk techno-functional properties in dairy applications. The isolation of MFGM from buttermilk improved its functionality while also recovering the MFGM bioactive components. Hydroxyapatite (HA) can be used to extract MFGM by adsorption via charged site interactions. However, the affinity of HA to MFGM or the main buttermilk proteins (casein micelles (CM), β-lactoglobulin (β-lg) and α-lactalbumin (α-lac)) is not known. The influence of important physicochemical parameters such as pH and temperature on these interactions is also unclear. For each buttermilk component, a quartz crystal microbalance diffusion analysis was performed to determine the maximum adsorption time and the attached mass density on HA-coated gold sensors. The influence of pH, ionic strength (IS), and temperature (T) on the affinity of each buttermilk component for HA particles was assessed using a 3-levels and 3-factors Box-Behnken design. The absorption rate was highest for the CM, followed by β-lg and α-lac, and then by the MFGM. Nevertheless, the final maximal attached mass densities to the HA were similar for the MFGM and CM, and 2.5 times higher than for β-lg and α-lac. This difference can be explained by the higher number of binding sites found in CM and their heavier mass. The model obtained by the Box-Behnken design plan showed that the adsorption of the CM changed with T, pH and IS. These results suggest that the techno-functional properties of buttermilk may be restored by specifically extracting MFGM with HA. Experiments are ongoing to determine conditions for fractionating MFGM directly from buttermilk.
PubMed: 38490551
DOI: 10.3168/jds.2024-24353