Current Knowledge About the Impact of Maternal and Infant Nutrition on the Development of the Microbiota-Gut-Brain Axis.

The prenatal and early postnatal periods are stages during which dynamic changes and the development of the brain and gut microbiota occur, and nutrition is one of the most important modifiable factors that influences this process. Given the bidirectional cross talk between the gut microbiota and the brain through the microbiota-gut-brain axis (MGBA), there is growing interest in evaluating the potential effects of nutritional interventions administered during these critical developmental windows on gut microbiota composition and function and their association with neurodevelopmental outcomes. We review recent preclinical and clinical evidence from animal studies and infant/child populations. Although further research is needed, growing evidence suggests that different functional nutrients affect the establishment and development of the microbiota-gut-brain axis and could have preventive and therapeutic use in the treatment of neuropsychiatric disorders. Therefore, more in-depth knowledge regarding the effect of nutrition on the MGBA during critical developmental windows may enable the prevention of later neurocognitive and behavioral disorders and allow the establishment of individualized nutrition-based programs that can be used from the prenatal to the early and middle stages of life.

Identification and anti-oxidative potential of milk fat globule membrane (MFGM)-derived bioactive peptides released through in vitro gastrointestinal digestion.

This study investigated the stability of milk fat globule membrane (MFGM) protein under simulated gastrointestinal conditions using an in vitro enzymatic digestion method. The optimal hydrolysis conditions were determined by monitoring the changes in particle size and zeta-potential of MFGM protein hydrolysates over time. Furthermore, the distribution of small molecular weight peptides with antioxidant activity was explored through DEAE-52 combined with in vitro cell experiments. Two novel antioxidant peptides (TGIIT and IITQ) were identified based on molecular docking technology and evaluated their potential scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+) radicals. TGIIT and IITQ also demonstrated remarkable abilities in promoting mitochondrial biogenesis and activating Keap1/Nrf2 signaling pathway, which can effectively counteract skeletal muscle dysfunction induced by oxidative stress. Thus, MFGM-derived antioxidant peptides have the potential to be employed in food to regulate muscle protein metabolism and alleviate sarcopenia.

Milk polar lipids composition and functionality: a systematic review.

Polar lipids including glycerophospholipids and sphingophospholipids are important nutrients and milk is a major source, particularly for infants. This systematic review describes the human and bovine milk polar lipid composition, structural organization, sources for formulation, and physiological functionality. A total of 2840 records were retrieved through Scopus, 378 were included. Bovine milk is a good source of polar lipids, where yield and composition are highly dependent on the choice of dairy streams and processing. In milk, polar lipids are organized in the milk fat globule membrane as a tri-layer encapsulating triglyceride. The overall polar lipid concentration in human milk is dependent on many factors including lactational stage and maternal diet. Here, reasonable ranges were determined where possible. Similar for bovine milk, where differences in milk lipid concentration proved the largest factor determining variation. The role of milk polar lipids in human health has been demonstrated in several areas and critical review indicated that brain, immune and effects on lipid metabolism are best substantiated areas. Moreover, insights related to the milk fat globule membrane structure-function relation as well as superior activity of milk derived polar lipid compared to plant-derived sources are emerging areas of interest regarding future research and food innovations.

MFGM components promote gut Bifidobacterium growth in infant and in vitro.

PURPOSE: Infant gut microbiota which plays an important role in long-term health is mainly shaped by early life nutrition. However, the effect of nutrients on infants gut microbiota is less researched. Here, we present a study aiming to investigate in vitro a modified formula that is supplemented with milk fat globule membrane (MFGM) that were missing in common formulas when compared with human milk and to assess the impact of feeding scheme on microbiota and metabolism. METHODS: A total of 44 infants including 16 from breast milk feeding, 13 from common formula feeding and 15 from modified formula feeding were analyzed, and A cross-sectional sampling of fecal and urine was done at 1 month-of-age. Stool microbiota composition was characterized using high-throughput DNA sequencing, and urinary metabolome was profiled by nuclear magnetic resonance (NMR). In vitro growth experiment of Bifidobacterium with key components from MFGM was performed and analyzed by both DNA and RNA. RESULTS: Stool samples from the infants who were breastfed had a higher relative abundance of Bifidobacterium and a lower relative abundance of Escherichia than the formula-fed infants. The stool microbiome shifts were associated with urine metabolites changes. Three substances including lactadherin, sialic acid and phospholipid, key components of MFGM were significantly positively correlated to Bifidobacterium of stool samples from infants, and stimulated the growth rate of Bifidobacterium significantly by provided energy in vitro growth experiment with RNA analysis. CONCLUSIONS: These findings suggest that the key components from MFGM could improve infants' health by modulating the gut microbiome, and possibly supporting the growth of Bifidobacterium. REGISTRATION: Clinicaltrials.gov NCT02658500 (registered on January 20, 2016).

Reduction of multiple reaction monitoring protein target list using correlation analysisa.

High mass resolution mass spectrometry provides hundreds to thousands of protein identifications per sample, and quantification is typically performed using label-free quantification. However, the gold standard of quantitative proteomics is multiple reaction monitoring (MRM) using triple quadrupole mass spectrometers and stable isotope reference peptides. This raises the question how to reduce a large data set to a small one without losing essential information. Here we present the reduction of such a data set using correlation analysis of bovine dairy ingredients and derived products. We were able to explain the variance in the proteomics data set using only 9 proteins across all major dairy protein classes: caseins, whey, and milk fat globule membrane proteins. We term this method Trinity-MRM. The reproducibility of the protein extraction and Trinity-MRM methods was shown to be below 5% in independent experiments (multi-day single-user and single-day multi-user) using double cream. Further application of this reductionist approach might include screening of large sample cohorts for biologically interesting samples before analysis by high-resolution mass spectrometry or other omics methodologies.

Effect of feeding mode on infant growth and cognitive function: study protocol of the Chilean infant Nutrition randomized controlled Trial (ChiNuT).

BACKGROUND: A central aim for pediatric nutrition is to develop infant formula compositionally closer to human milk. Milk fat globule membranes (MFGM) have shown to have functional components that are found in human milk, suggesting that addition of bovine sources of MFGM (bMFGM) to infant formula may promote beneficial outcomes potentially helping to narrow the gap between infants who receive human breast milk or infant formula. The objective of the current study is to determine how the addition of bMFGM in infant formula and consumption in early infancy affects physical growth and brain development when compared to infants fed with a standard formula and a reference group of infants fed with mother's own milk. METHODS: Single center, double-blind, and parallel randomized controlled trial. Planned participant enrollment includes: infants exclusively receiving breast milk (n = 200; human milk reference group; HM) and infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age (n = 340). The latter were randomized to receive one of two study formulas until 12 months of age: 1) cow's milk based infant formula that had docosahexaenoic (DHA) (17 mg/100 kcal) and arachidonic acid (ARA) (25 mg/100 kcal); 1.9 g protein/100 kcal; 1.2 mg Fe/100 kcal (Standard formula; SF) or 2) a similar infant formula with an added source of bovine MFGM (whey protein-lipid concentrate (Experimental formula; EF). Primary outcomes will be: 1) Physical growth (Body weight, length, and head circumference) at 730 days of age; and 2) Cognitive development (Auditory Event-Related Potential) at 730 days of age. Data will be analyzed for all participants allocated to each study feeding group. DISCUSSION: The results of this study will complement the knowledge regarding addition of bMFGM in infant formula including support of healthy growth and improvement of neurodevelopmental outcomes. TRIAL REGISTRATION: NCT02626143, registered on December 10th 2015.

Omics analysis reveals variations among commercial sources of bovine milk fat globule membrane.

Milk fat globule membrane (MFGM) is a glycosylated, protein-embedded, phospholipid fraction that surrounds triglycerides in milk. Commercial bovine sources have recently come to the market as a novel food ingredient and have been added to various products, including infant formula. Considering that MFGM is a heterogeneous mixture of fat, protein, and carbohydrate, it can be expected that variations among MFGM products exist. For this reason, our aim was to characterize the composition of commercial MFGM samples through a combination of proteomic and lipidomic analyses. Six bovine milk fractions, represented as MFGM fractions or phospholipid fractions, were obtained from various commercial sources. Additionally, the MFGM samples were compared with 2 infant formulas, a standard formula as well as a premium formula containing MFGM. For proteomic analysis, bottom-up data-dependent liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on each MFGM fraction, and nearly a thousand proteins were identified across all samples, with 364 of them having different abundance across the samples tested. One hundred twelve proteins differed by a fold-change of 10 or greater, 14 by a fold-change of 50, and 2 by a fold-change of 100 in at least 1 pair, suggesting large differences in the proteins present in these fractions. Even though the classical MFGM proteins were enriched in the MFGM fractions, the relative protein composition varied considerably, and all contain an abundance of milk (casein and whey) proteins. Lipidomic analysis identified a total of 393 lipid species across both positive and negative ionization modes, with the major classes detected being triglycerides, sphingomyelins, and several phospholipids. Across all samples, triglycerides comprised at least 50% of total lipids, with phosphatidylcholine and sphingomyelin being the second and third most abundant lipid classes, respectively. These findings demonstrate the heterogeneous nature of various bovine commercial MFGM fractions. This variation must be considered when evaluating and describing potential functional benefits of these products shown in clinical trials.

Comparative Analysis of Milk Fat Globular Membrane (MFGM) Proteome between Saudi Arabia Camelus dromedary Safra and Wadha Breeds.

Camel milk is traditionally known to have medicinal properties and many potential health benefits. Natural milk contains many soluble proteins and nanoparticles, such as a milk fat globule membrane (MFGM), a three-layered membrane covering of milk fat globule mainly composed of proteins and lipids, which plays an important role in human health. MFGM proteins account for 1%-4% of total milk proteins, and their nutritive value and distribution depends on the different breeds. The differential composition of these membrane proteins among different camel breeds has not been explored. The current study, therefore, aimed to quantitatively analyze and compare the MFGM proteome between the milk produced by the two most common Saudi camel breeds, Camelus dromedarius: Safra and Wadha. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analysis revealed a total of 44 MFGM proteins that were identified with a significant difference in abundance (p ≤ 0.05; fold change ≥ 1.5) between the two breeds. Thirty-one proteins were up-regulated and 13 proteins were down-regulated in the Safra breed compared to the Wadha breed. The proteins identified with an increased abundance included α-lactalbumin, lactadherin, and annexin a8, whereas the down-regulated proteins included butyrophilin subfamily 1 member a1, lactotransferrin, and vinculin. The differentially abundant proteins were analyzed by the UNIPROT system and gene ontology (GO) to reveal their associations with known biological functions and pathways. Enzyme-linked immunosorbent assay (ELISA) confirmed the 2D-DIGE findings of butyrophilin (BTN) and α-lactalbumin (α-LA) levels obtained from Safra and Wadha breeds.

Qualitative and Quantitative Study of Glycosphingolipids in Human Milk and Bovine Milk Using High Performance Liquid Chromatography-Data-Dependent Acquisition-Mass Spectrometry.

Cerebrosides (Crb; including glucosylceramide and galactosylceramide) and lactosylceramide (LacCer) are structurally complex lipids found in many eukaryotic cell membranes, where they play important roles in cell growth, apoptosis, cell recognition and signaling. They are also found in mammalian milk as part of the milk fat globule membrane (MFGM), making milk an important dietary component for the rapidly growing infant. This study reports the development of a robust analytical method for the identification and characterization of 44 Crb and 23 LacCer molecular species in milk, using high performance liquid chromatography-tandem mass spectrometry in data-dependent acquisition mode. For the first time, it also compares the distributions of these species in human and bovine milks, a commercial MFGM-enriched dairy ingredient (MFGM Lipid 100) and commercial standards purified from bovine milk. A method for quantifying Crb and LacCer in milk using mass spectrometry in neutral loss scan mode was developed and validated for human milk, bovine milk and MFGM Lipid 100. Human milk was found to contain approximately 9.9-17.4 µg Crb/mL and 1.3-3.0 µg LacCer/mL, whereas bovine milk (pooled milk from a Friesian herd) contained 9.8-12.0 and 14.3-16.2 µg/mL of these lipids, respectively. The process used to produce MFGM Lipid 100 was shown to have enriched these components to 448 and 1036 µg/g, respectively. No significant changes in the concentrations of both Crb and LacCer were observed during lactation.

Valorisation of Whey and Buttermilk for Production of Functional Beverages - An Overview of Current Possibilities.

Whey and buttermilk are the main by-products of the dairy industry, both having excellent nutritional properties. Buttermilk contains a unique component, the milk fat globule membrane (MFGM). MFGM contains bioactive compounds with positive health effects like antitumour or cholesterol-lowering impact. Whey proteins are found in whey and are a source of bioactive peptides acting positively on coronary, gastrointestinal, immune and nervous systems. Yet, buttermilk and whey are insufficiently utilized in functional food production. Various technological solutions have been studied in order to increase the production of foods based on whey and/or buttermilk whereby the production of beverages appear to be most acceptable from the economic and technological point +of view. Thus, the aim of this paper is to give an overview of current knowledge about the possibilities of creating whey and/or buttermilk beverages.

Complex lipid globules in early-life nutrition improve long-term metabolic phenotype in intra-uterine growth-restricted rats.

Intra-uterine growth restriction (IUGR) is associated with adverse metabolic outcome later in life. Healthy mice challenged with a Western-style diet (WSD) accumulated less body fat when previously fed a diet containing large lipid globules (complex lipid matrix (CLM)). This study was designed to clarify whether an early-life CLM diet mitigates 'programmed' visceral adiposity and associated metabolic sequelae after IUGR. In rats, IUGR was induced either by bilateral uterine vessel ligation (LIG) or sham operation (i.e. intra-uterine stress) of the dam on gestational day 19. Offspring from non-operated (NOP) dams served as controls. Male offspring of all groups were either fed CLM or 'normal matrix' control diet (CTRL) from postnatal days (PND) 15 to 42. Thereafter, animals were challenged with a mild WSD until dissection (PND 98). Fat mass (micro computer-tomograph scan; weight of fat compartments), circulating metabolic markers and expression of 'metabolic' genes (quantitative real-time PCR) were assessed. CLM diet significantly reduced visceral fat mass in LIG at PND 40. At dissection, visceral fat mass, fasted blood glucose, TAG and leptin concentrations were significantly increased in LIG-CTRL v. NOP-CTRL, and significantly decreased in LIG-CLM v. LIG-CTRL. Gene expression levels of leptin (mesenteric fat) and insulin-like growth factor 1 (liver) were significantly reduced in LIG-CLM v. LIG-CTRL. In conclusion, early-life CLM diet mitigated the adverse metabolic phenotype after utero-placental insufficiency. The supramolecular structure of dietary lipids may be a novel aspect of nutrient quality that has to be considered in the context of primary prevention of obesity and metabolic disease in at-risk populations.

Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood.

Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with phospholipids (PL) (Nuturis®; PL of milk fat globule membrane (MFGM) fraction origin) in early life protected against excessive body fat accumulation following a diet challenge in adult life. We now set out to determine the relevance of increased droplet size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in adult life. From day 16 to 42, male mouse pups were exposed to diets with small (S) or large (L) lipid droplets (0·3 v. 2·9 µm average mode diameter, respectively), either without MFGM or with MFGM coating around the lipid droplet, resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis® IMF diet). Mice were subsequently challenged with a Western-style diet until dissection at postnatal day 98. A non-challenged group served as reference (REF). We repeatedly determined body composition between postnatal day 42 and 98. At day 98 plasma and gene expression measurements were performed. Only the Nuturis® IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets reduced body fat mass to a level comparable with the REF group. These data support the notion that the structural aspects of lipids in human milk, for example, both lipid droplet size as well as the MFGM coating, may contribute to its reported protective effect against obesity in later life.

Dairy food products: good or bad for cardiometabolic disease?

Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction. However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved, but how they may be beneficially influenced during milk production and processing.

Safety evaluation of the consumption of high dose milk fat globule membrane in healthy adults: a double-blind, randomized controlled trial with parallel group design.

Consumption of milk fat globule membrane (MFGM) in combination with habitual exercise suppresses age-associated muscle loss. The effects of high dose MFGM, however, are not known. A double-blind, randomized controlled trial with parallel group design was conducted to evaluate the safety of consuming high dose MFGM tablets. The subjects were 32 healthy adult men and women. Subjects were given 5 times the recommended daily intake of the tablets containing 6.5 g of MFGM or whole milk powder for 4 weeks. Stomach discomfort and diarrhea were observed; however, these symptoms were transitory and slight and were not related to consumption of the test tablets. In addition, there were no clinically significant changes in anthropometric measurements or blood tests. Total degree of safety assessed by the physicians of all subjects was "safe." These findings suggest that consumption of the tablets containing 6.5 g MFGM for 4 weeks is safe for healthy adults.

Detection and characterisation of Complement protein activity in bovine milk by bactericidal sequestration assay.

While the Complement protein system in human milk is well characterised, there is little information on its presence and activity in bovine milk. Complement forms part of the innate immune system, hence the importance of its contribution during milk ingestion to the overall defences of the neonate. A bactericidal sequestration assay, featuring a Complement sensitive strain, Escherichia coli 0111, originally used to characterise Complement activity in human milk was successfully applied to freshly drawn bovine milk samples, thus, providing an opportunity to compare Complement activities in both human and bovine milks. Although not identical in response, the levels of Complement activity in bovine milk were found to be closely comparable with that of human milk. Differential counts of Esch. coli 0111 after 2 h incubation were 6.20 and 6.06 log CFU/ml, for raw bovine and human milks, respectively - the lower value representing a stronger Complement response. Exposing bovine milk to a range of thermal treatments e.g. 42, 45, 65, 72, 85 or 95 °C for 10 min, progressively inhibited Complement activity by increasing temperature, thus confirming the heat labile nature of this immune protein system. Low level Complement activity was found, however, in 65 and 72 °C heat treated samples and in retailed pasteurised milk which highlights the outer limit to which high temperature, short time (HTST) industrial thermal processes should be applied if retention of activity is a priority. Concentration of Complement in the fat phase was evident following cream separation, and this was also reflected in the further loss of activity recorded in low fat variants of retailed pasteurised milk. Laboratory-based churning of the cream during simulated buttermaking generated an aqueous (buttermilk) phase with higher levels of Complement activity than the fat phase, thus pointing to a likely association with the milk fat globule membrane (MFGM) layer.

MFGM-enriched whey displays antiviral activity against common pediatric viruses in vitro.

Background: Among the most common mucosal viral infections in infants are rotavirus, one of the main causes of severe gastroenteritis in infants and children up to 5 years, and respiratory syncytial virus (RSV), one of the leading causes of lower respiratory tract infections. Both human milk and bovine milk derived factors may provide protection against mucosal viral infections. More recently, a similar activity of milk derived proteins was suggested for SARS-CoV-2. The goal of the current study was to test antiviral activity of the bovine milkfat globule membrane (MFGM) against rotavirus, RSV and SARS-CoV-2 and to further characterize MFGM-enriched whey to identify which components in MFGM-enriched whey may contribute to the inhibitory activity. Methods: The effects of MFGM-enriched whey, its whey protein isolate counterpart (WPI, obtained from the same production process) and a conventional whey protein concentrate (WPC) on rotavirus (strains Wa and SA114F), RSV (strain RSV-A2) and SARS-CoV-2 (Alpha variant) infectivity were determined using MA104 cells, human alveolar basal epithelial (A549) cells and monkey kidney (Vero E6) cells, respectively. The compounds were characterized in detail by LC-MS/MS and 31P-NMR to determine protein and phospholipid composition, respectively. Results: Relative to its WPI counterpart, MFGM-enriched whey demonstrated a dose-dependent inhibition for both rotavirus and RSV whereas for SARS-CoV-2 inhibition was only observed at the highest concentration tested. Label-free quantification (LFQ) and intensity based absolute quantification (iBAQ) of identified proteins revealed a clear difference between MFGM-enriched whey and its controls including enrichment of known MFGM proteins and non-MFGM proteins that are enriched simultaneously, some of which have previously been demonstrated to display anti-viral activity. Although not completely absent from other whey protein preparations, MFGM-enriched whey had the highest specific and total phospholipid levels. Conclusion: MFGM-enriched whey displayed antiviral activity against multiple viruses of clinical importance. This study provides insights into the active components in MFGM-enriched whey and may contribute to previous clinical observations with MFGM-enriched formula demonstrating reduced respiratory and gastrointestinal infections in formula fed infants.

Phosphoproteomics Revealed Differentially Expressed Sites and Function of the Bovine Milk Fat Globule Membrane in Colostrum and Mature Milk.

One type of large and intricate post-translational modification of milk proteins that has significant biological implications is phosphorylation. The characterization of phosphoproteins found in the bovine milk fat globule membrane (MFGM) is still mostly unknown. Here, label-free phosphoproteomics was used to identify 94 phosphorylation sites from 54 MFGM phosphoproteins in bovine colostrum (BC) and 136 phosphorylation sites from 91 MFGM phosphoproteins in bovine mature milk (BM). αs1-Casein and ß-casein were the most phosphorylated proteins in bovine colostrum. In bovine mature milk, perilipin-2 was the protein with the greatest number of phosphorylation sites. The results show that bovine colostrum MFGM phosphoproteins were mainly involved in immune function, whereas bovine mature MFGM phosphoproteins were mainly involved in metabolic function. Plasminogen and osteopontin were the most strongly interacting proteins in colostrum, whereas perilipin-2 was the most strongly interacting protein in bovine mature milk. This work demonstrates the unique alterations in the phosphorylation manner of the bovine MFGM protein during lactation and further expands our knowledge of the site characteristics of bovine MFGM phosphoproteins. This result confirms the value of MFGM as a reference ingredient for infant formula during different stages.

A novel approach to insulin delivery via oral route: Milk fat globule membrane derived liposomes as a delivery vehicle.

The current research endeavor seeks to unlock the potential of orally administered insulin formulations by utilizing liposomes derived from the fat globule membrane (MFGM) of camel milk as carriers for insulin. This pursuit emerges as a result of the recognized limitations of subcutaneous insulin therapy. The liposomes were meticulously created using the thin film hydration method, followed by comprehensive chemical and morphological analyses. Additionally, comprehensive safety assessments were carried out in vitro and in vivo, revealing significant findings. The Fourier-transform infrared (FTIR) spectrum confirmed the presence of insulin within the liposomes, demonstrating changes in their size and charge. The in vitro cytotoxicity analysis, performed on HEK-293 cell lines through the MTT assay, yielded results indicating a cell viability of over 90%. In the in vivo investigation, diabetic rats induced by STZ were utilized to evaluate the effects of the liposomes, revealing substantial reductions in blood glucose levels, bilirubin, alkaline phosphatase (ALP), albumin, and alanine aminotransferase (ALT) levels. Hepatic histopathological assessments showed signs of recovery across all treatment groups, with no observable microscopic changes in renal tissue. This investigation highlights the significant hypoglycemic effects observed in insulin-loaded liposomes derived from MFGM obtained from camel milk when administered orally.

Milk Fat Globule Membrane-Containing Protein Powder Promotes Fitness in Caenorhabditis elegans.

Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilized Caenorhabditis elegans to elucidate how MFGM-containing protein powder (MProPow), previously used in a clinical trial, affect the physiology of this model organism. Our results demonstrate that MProPow does not affect lifespan but promotes the fitness of the animals. Surprisingly, gene expression analysis revealed that MProPow decreases the expression of genes functioning on innate immunity, which also translates into reduced survival on pathogenic bacteria. One of the innate immunity-associated genes showing reduced expression upon MProPow supplementation is cpr-3, the homolog of human cathepsin B. Interestingly, knockdown of cpr-3 enhances fitness, but not in MProPow-treated animals, suggesting that MProPow contributes to fitness by downregulating the expression of this gene. In summary, this research highlights the value of C. elegans in testing the biological activity of food supplements and nutraceuticals. Furthermore, this study should encourage investigations into whether milk-derived peptides and MFGM mediate their beneficial effects through the modulation of cathepsin B expression in humans.

Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial.

BACKGROUND: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health. OBJECTIVES: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m2) trajectories and blood pressure at school age. METHODS: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit. RESULTS: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m2, 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m2, respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively. CONCLUSIONS: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538.