Bovine Milk Fat Globule Membrane Research Articles

Bovine and Goat Milk Fat Globule Membrane Supplementation Alleviates Autism-like Behavior by Modulating Lipid Metabolism and Gut Microbiota

Bovine and Goat Milk Fat Globule Membrane Supplementation Alleviates Autism-like Behavior by Modulating Lipid Metabolism and Gut Microbiota

Proteomic and phosphoproteomic reveal immune-related function of milk fat globule membrane in bovine milk of different lactation periods

Information regarding protein expression and phosphorylation modifications in the bovine milk fat globule membrane is scarce, particularly throughout various lactation periods. This study employed a complete proteome and phosphoproteome between bovine colostrum and mature milk. A total of 11 proteins were seen in both protein expression and phosphorylation levels. There were 400 proteins identified in only protein expression, and 104 phosphoproteins identified in only phosphorylation levels. A total of 232 significant protein characteristics were identified within the proteome and significant phosphorylation sites within 86 phosphoproteins of the phosphoproteome. Biological activities and pathways primarily exhibited associations with the immune system. Simultaneously, a comprehensive analysis of proteins and phosphorylation sites using a multi-omics approach. Hence, the data we have obtained has the potential to expand our understanding of how the bovine milk fat globule membrane might be utilized as a beneficial component in dairy products.

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 β-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.

Improved Neurodevelopmental Outcomes at 5.5 Years of Age in Children Who Received Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula Through 12 Months: A Randomized Controlled Trial

To evaluate neurodevelopmental outcomes at 5.5 years of age in children who were previously randomized to cow milk-based infant formula (control) or similar formula (milk fat globule membrane plus lactoferrin [MFGM+LF]) with added sources of bovine MFGM and bovine LF (bLF) through 12 months of age. Children who completed study feeding were invited to participate in follow-up assessments: cognitive development across multiple domains (primary outcome; Wechsler Preschool & Primary Scale of Intelligence™, 4th Edition; WPPSI™-IV), inhibitory control/rule learning (Stroop Task), flexibility/rule learning (Dimensional Change Card Sort; DCCS), and behavior/emotion (Child Behavior Checklist; CBCL). Of 292 eligible participants (Control: 148, MFGM+LF: 144), 116 enrolled and completed assessments (Control: 59, MFGM+LF: 57). There were no group demographic differences except family income (MFGM+LF significantly higher). WPPSI-IV composite scores (mean±SE) for Visual Spatial (100.6±1.7 vs 95.3±1.7; P=0.027), Processing Speed (107.1±1.4 vs 100.0±1.4; P<0.001), and Full Scale IQ (98.7±1.4 vs 93.5±1.5; P=0.012) were significantly higher for MFGM+LF vs Control, even after controlling for demographic/socioeconomic factors. Stroop Task scores were significantly higher in MFGM+LF vs control (P<0.001). Higher DCCS scores (P=0.013) in the border phase (most complex/challenging) were detected and more children passed the border phase (32% vs 12%; P=0.039) for MFGM vs control. No group differences in CBCL score were detected. Children who received infant formula to 12 months of age with added bMFGM and bLF vs standard formula demonstrated improved cognitive outcomes in multiple domains at 5.5 years of age, including measures of intelligence and executive function.

Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age-A randomized controlled trial.

We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age. A multi-center, randomized, controlled trial. Late preterm infants (34-37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA. The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF (n = 22) and STF (n = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, -1.63 to 5.18, P = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16-0.85), P = 0.02]. We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size. The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). "mailto:maria.makrides@sahmri.com" maria.makrides@sahmri.com.

Efficient in vitro digestion of lipids and proteins in bovine milk fat globule membrane ingredient (MFGMi) and whey-casein infant formula with added MFGMi

The relative immaturity of the infant digestive system has the potential to affect the bioavailability of dietary lipids, proteins, and their digested products. We performed a lipidomic analysis of a commercial bovine milk fat globule membrane ingredient (MFGMi) and determined the profile of lipids and proteins in the bioaccessible fraction after in vitro digestion of both the ingredient and whey-casein-based infant formula without and with MFGMi. Test materials were digested using a static 2-phase in vitro model, with conditions simulating those in the infant gut. The extent of digestion and the bioaccessibility of various classes of neutral and polar lipids were monitored by measuring a wide targeted lipid profile using direct infusion-mass spectrometry. Digestion of abundant proteins in the ingredient and whey-casein infant formula containing the ingredient was determined by denaturing PAGE with imaging of Coomassie Brilliant Blue stained bands. Cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, and phosphatidylethanolamines in MFGMi were hydrolyzed readily during in vitro digestion, which resulted in marked increases in the amounts of free fatty acids and lyso-phospholipids in the bioaccessible fraction. In contrast, sphingomyelins, ceramides, and gangliosides were largely resistant to simulated digestion. Proteins in MFGMi and the infant formulas also were hydrolyzed efficiently. The results suggest that neutral lipids, cholesterol esters, phospholipids, and proteins in MFGMi are digested efficiently during conditions that simulate the prandial lumen of the stomach and small intestine of infants. Also, supplementation of whey-casein-based infant formula with MFGMi did not appear to alter the profiles of lipids and proteins in the bioaccessible fraction after digestion.

Micronutrient, Metabolic, and Inflammatory Biomarkers through 24 Months of Age in Infants Receiving Formula with Added Bovine Milk Fat Globule Membrane through the First Year of Life: A Randomized Controlled Trial

BackgroundBovine milk fat globule membrane (MFGM) added in infant formula supports typical growth and safety through 24 mo of age in term infants. ObjectivesTo assess micronutrient (zinc, iron, ferritin, transferrin receptor), metabolic [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin-like growth factor-1 (IGF-1), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory (leptin, adiponectin, high sensitivity C-reactive protein) secondary outcomes through 24 mo of age in infants who received standard cow’s milk-based infant formula (SF), similar formula with added bovine MFGM (EF), or human milk (HM) through 1 y. MethodsInfants whose parents agreed to a blood draw at baseline (<120 d of age) (SF = 80; EF = 80; HM = 83) were included. Subsequent collections (2–4 h fasting) occurred at D180, D365, and D730. Biomarker concentrations were analyzed and group changes tested using generalized estimating equations models. ResultsOnly serum iron (+22.1 μg/dL) and HDL-C (+2.5 mg/dL) were significantly higher for EF compared with SF at D730. Prevalence of zinc deficiency for EF (-17.4%) and SF (-16.6%) at D180 and depleted iron stores for SF (+21.4%) at D180 and EF (-34.6%) and SF (-28.0%) at D365 were significantly different compared with HM. IGF-1 (ng/mL) for EF and SF was significantly higher at D180 (+8.9) and for EF (+8.8) at D365, and (+14.5) at D730 compared with HM. Insulin (μUI/mL) for EF (+2.5) and SF (+5.8) and HOMA-IR for EF (+0.5) and SF (+0.6) were significantly higher compared with HM at D180. TGs (mg/dL) for SF (+23.9) at D180, for EF (+19.0) and SF (+17.8) at D365, and EF (+17.3) and SF (+14.5) at D730 were significantly higher compared with HM. Zinc, ferritin, glucose, LDL-C and total cholesterol changes were higher in formula groups compared with HM between various time points. ConclusionsMicronutrient, metabolic, and inflammatory biomarkers were generally similar through 2 y in infants who received infant formula with or without added bovine MFGM. Over the 2 y, differences were observed between infant formulas and HM reference group. This trial was registered at clinicaltrials.gov as NTC02626143.

Serotype-dependent adhesion of Shiga toxin-producing Escherichia coli to bovine milk fat globule membrane proteins.

Shiga toxin-producing Escherichia coli (STEC) are food-borne pathogens that can cause severe symptoms for humans. Raw milk products are often incriminated as vehicule for human STEC infection. However, raw milk naturally contains molecules, such as the milk fat globule membrane and associated proteins, that could inhibit pathogen adhesion by acting as mimetic ligands. This study aimed to: (i) evaluate the capability of STEC cells to adhere to bovine milk fat globule membrane proteins (MFGMPs), (ii) highlight STEC surface proteins associated with adhesion and (iii) evaluate the variation between different STEC serotypes. We evaluated the physicochemical interactions between STEC and milk fat globules (MFGs) by analyzing hydrophobic properties and measuring the ζ-potential. We used a plate adhesion assay to assess adhesion between MFGMPs and 15 Escherichia coli strains belonging to three key serotypes (O157:H7, O26:H11, and O103:H2). A relative quantitative proteomic approach was conducted by mass spectrometry to identify STEC surface proteins that may be involved in STEC-MFG adhesion. The majority of E. coli strains showed a hydrophilic profile. The ζ-potential values were between -3.7 and - 2.9 mV for the strains and between -12.2 ± 0.14 mV for MFGs. Our results suggest that non-specific interactions are not strongly involved in STEC-MFG association and that molecular bonds could form between STEC and MFGs. Plate adhesion assays showed a weak adhesion of O157:H7 E. coli strains to MFGMPs. In contrast, O26:H11 and O103:H2 serotypes attached more to MFGMPs. Relative quantitative proteomic analysis showed that the O26:H11 str. 21,765 differentially expressed five outer membrane-associated proteins or lipoproteins compared with the O157:H7 str. EDL933. This analysis also found strain-specific differentially expressed proteins, including four O26:H11 str. 21,765-specific proteins/lipoproteins and eight O103:H2 str. PMK5-specific proteins. For the first time, we demonstrated STEC adhesion to MFGMPs and discovered a serotype effect. Several outer membrane proteins-OmpC and homologous proteins, intimin, Type 1 Fimbriae, and AIDA-I-that may be involved in STEC-MFG adhesion were highlighted. More research on STEC's ability to adhere to MFGMs in diverse biological environments, such as raw milk cheeses and the human gastrointestinal tract, is needed to confirm the anti-adhesion properties of the STEC-MFG complex.

Comparison of milk fat globule membrane protein profile among bovine, goat and camel milk based on label free proteomic techniques

Milk fat globule membrane (MFGM) proteins, which are recognized to play a variety of biological roles; nevertheless, their composition and interspecies complexity remain unknown. This study aimed to identify and quantify proteins extracted from MFGM-enriched fractions of bovine, goat and camel milk by a label free proteomics approach. We identified 1579 proteins, substantially increasing the number of MFGM proteins identified for these species. The results of functional analysis showed that the identified MFGM proteins had similar functional annotations, with cellular processes, intracellular anatomical structures and binding being the predominant GO annotations. And most of the proteins were involved in KEGG pathways such as protein processing of ribosomes and endoplasmic reticulum. Subsequently, multiple statistical methods were used to compare the differences in MFGM protein quantification among different species. The results of principal component analysis showed that bovine, goat and camel milk MFGM proteins were significantly different, among which CSN1S1, XDH, LTF and PI4KA played an important role in taxonomic identification. Meanwhile the results of hierarchical clustering showed that the differences (p < 0.05) between bovine and goat milk were smaller than those of camel milk. These new data deepen the understanding of the protein composition of MFGM and its possible physiological roles, providing directions for the production of specific functional milk proteins.

The Immunological Role of Milk Fat Globule Membrane.

Human milk is the ideal food for newborns until the age of six months. Human milk can be defined as a dynamic living tissue, containing immunological molecules, such as immunoglobulins, supra-molecular structures, such as the milk fat globule membrane (MFGM), and even entire cells, such as the milk microbiota. The milk composition changes throughout lactation to fulfill the infant's requirements and reflect the healthy/disease status of the lactating mother. Many bioactive milk components are either soluble or bound to the MFGM. In this work, we focus on the peculiar role of the MFGM components, from their structural organization in fat globules to their route into the gastrointestinal tract. Immunometabolic differences between human and bovine MFGM components are reported and the advantages of supplementing infant formula with the MFGM are highlighted.

Lipidome Analysis in Brain and Peripheral Plasma Following Milk Fat Globule Membrane Supplementation in Rodents.

Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigates bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induces parallel changes to plasma and brain lipidomes. Transgenic APOE*3.Leiden mice (n = 18 per group) and Sprague-Dawley rats (n = 12 per group) are fed bMFGM-enriched (MFGM+) or Control diet, followed by phospholipid profile-determination in plasma, hippocampus, and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrates a separation between MFGM+ and Control plasma across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) are consistently higher in the circulation of MFGM+ groups. A similar trend is observed in rat prefrontal cortex, although no significant separation of the brain lipidome is demonstrated. bMFGM-enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with similar, but non-significant, trends in central brain regions. These changes may contribute to the beneficial effects of bMFGM on neurodevelopment during early life.

Profiling of phospholipid classes and molecular species in human milk, bovine milk, and goat milk by UHPLC-Q-TOF-MS

This study aimed to identify differences of lipidome and fatty acid composition among human, bovine and caprine milk fat globule membrane (MFGM) using a lipidomics approach. In total, 11 lipid classes were determined, including PC, PE, SM, PG, PI, PS, Cer, PA, HexCer, Hex2Cer and CL. Using positive and negative ionization modes, 73 and 156 common significantly differential lipid species were identified in three typical MFGM. The oleic acid (C18:1) was the dominant fatty acid in human (28.29 ± 0.04 g/100 g) and caprine (35.71 ± 0.02 g/100 g) MFGM, whereas Palmitic acid (C16:0, 29.13 ± 0.07 g/100 g) was the dominant fatty acid in bovine MFGM. In addition, there was no significant difference in long chain fatty acids between human MFGM and caprine milk. Overall, the results provide essential insights into differential lipids characterization in MFGM, along with a theoretical basis for the design of new infant formula.

Efficient In Vitro Digestion of Lipids and Proteins in Bovine Milk Fat Globule Membrane (MFGM) Ingredient and Infant Formula Containing MFGM

ObjectivesThe relative immaturity of the infant digestive system after birth has the potential to affect the bioaccessibility of dietary lipids, proteins and their digested product. The in vitro digestion of lipids and protein in bovine milk fat globule membrane (MFGM) ingredient and infant formula without and with MFGM ingredient (bovine source), as well as the partitioning of non-digested and products of digestion in bioaccessible fraction of chyme were measured. Conditions that simulate those in the stomach and small intestine of infants were used.MethodsMFGM ingredient and whey/casein-based infant formula with and without 6%MFGM ingredient were digested using static, two-phase in vitro digestion model with conditions simulating those in the infant gut. Digestion and bioaccessibility of lipids were monitored by measuring a wide lipid profile using direct infusion-mass spectrometry (DI-MS/MS). Digestion of proteins were determined by denaturing polyacrylamide gel electrophoresis, with quantitative imaging of all blue stained bands.ResultsCholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, and phosphatidylethanolamines in the MFGM ingredients were readily hydrolyzed resulting in marked increases in the amounts of free fatty acids and lyso-phospholipids in the bioaccessible fraction of chyme. In contrast, sphingomyelins, ceramides and GM3 gangliosides were relatively resistant to digestion. Protein in MFGM ingredient and infant formula without and with added MFGM ingredient also were efficiently digested.ConclusionsThe results suggest proteins, neutral lipids and phospholipids in MFGM are efficiently digested using conditions that simulate those in the prandial lumen of the stomach and small intestine of infants. Also, the profile of lipid and protein digestion is similar for whey/casein-based infant formula without and with MFGM ingredient using conditions that simulate those in the infant gut.Funding SourcesOhio State Agriculture Research and Development Center, the JT Parker Endowment and Reckitt Nutrition Institute.

A synbiotics, long chain polyunsaturated fatty acids, and milk fat globule membranes supplemented formula modulates microbiota maturation and neurodevelopment

The critical window of concurrent developmental paths of the nervous system and gut microbiota in infancy provides an opportunity for nutritional interventions with potential health benefits later in life. We compared the dynamics of gut microbiota maturation and explored its association with neurodevelopment at 12 months and 4 years of age in 170 full-term healthy infants fed a standard formula (SF) or a new formula (EF) based on standard formula supplemented with synbiotics, long chain polyunsaturated fatty acids (LC-PUFA) and bovine milk fat globule membranes (MFGM), including a breastfed reference group (BF). Using Dirichlet Multinomial Modelling, we characterized three microbial enterotypes (Mixed, anaerobic and aerobic profile; Bact, Bacteroides-dominant; Firm, Firmicutes-enriched) and identified a new enterotype dominated by an unidentified genus within Lachnospiraceae (U_Lach). Enterotypes were associated with age (Mixed with baseline, U_Lach with month 6, Bact and Firm with months 12 and 18). Trajectories or timely enterotype shifts in each infant were not random but strongly associated with type of feeding. Trajectories in SF shifted from initial Mixed to U_Lach, Bact or Firm at month. Microbiota maturation in EF split into a fast trajectory as in SF, and a slow trajectory with Mixed to U_Lach, Bact or Firm transitions at months 12 or 18, as in BF. EF infants with slow trajectories were more often in-home reared and born by vaginal delivery to mothers with pre-pregnancy lean BMI. At 12 months of age, language and expressive language scores were significantly higher in EF infants with fast trajectories than in BF. Neurodevelopmental outcomes were similar between EF infants with slow trajectories and BF at 12 months and 4 years of age. Feeding a synbiotics, LC-PUFA and MFGM supplemented formula in a specific infant environment promoted probiotic growth and retarded gut microbiota maturation with similar neurodevelopment outcomes to breastfed infants. NCT02094547.

Added bovine milk fat globule membrane in formula: Growth, body composition, and safety through age 2: An RCT

ObjectiveThe aim of this study was to assess the effects of an experimental formula (EF) with added whey protein-lipid concentrate (5 g/L; source of bovine milk fat globule membrane [bMFGM]) on growth, body composition, and safety through 24 mo of age in term infants. MethodsThis was a double-blinded, randomized controlled trial conducted in Santiago, Chile. Infants were enrolled before 120 d and randomized to receive standard cow's milk-based formula (SF) or EF through the first year of life. Breastfed infants were the reference (HM). Growth (weight-for-age [WAZ], length-for-age [LAZ], BMI-for-age [BAZ], headcircumference-for-age [HCZ] z-scores); body composition (fat mass [FM] and fat-free mass, percentage body fat [%BF]); and adverse events through day 730 were recorded. Outcome trajectories were analyzed using a single generalized estimating equation testing the interaction between group and visit. ResultsWe recruited 582 infants (HM = 235; SF = 174; EF = 173); 478 (>80%) completed the study. At baseline, only WAZ was different between the formula groups (0.14 lower in EF versus SF group, P = 0.035). WAZ, LAZ, and BAZ trajectories were higher from baseline to days 365 and 730 in EF or SF compared with HM (all P < 0.05). No differences in changes in body composition were observed between the formula groups. For EF versus HM, %BF was lower at day 180; however, this difference reversed from day 365. Fat-free mass was higher in formula groups compared with HM at all time points. No group difference in adverse event incidence rate was detected. ConclusionDuring the first 2 y of life, infant formula with added bMFGM supports typical growth and safety compared with a standard formula.

Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial.

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow’s milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow’s milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14–120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14–120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow’s milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.

Milk fat as a source of bioactive compounds

Milk fat as a source of bioactive compounds

Neurodevelopmental outcomes of healthy Chinese term infants fed infant formula enriched in bovine milk fat globule membrane for 12 months - A randomized controlled trial.

Human milk fat globule membrane (MFGM) has multifunctional health benefits. We evaluated neurodevelopment and growth of healthy term infants fed bovine milk-derived MFGM-enriched formula (MF) over 12 months. A prospective, multi-center, double-blind, randomized trial was conducted in Fuzhou, China. Healthy term infants (n=212), aged <14 days, were assigned randomly to be fed MF or a standard formula (SF) for 6 months and then switched to stage 2 MF and SF formula until 12 months. A reference group (n=206) contained healthy breastfed infants (BFR). Neurodevelopment was assessed with Bayley-III Scales. At 12 months, the composite social emotional (+3.5) and general adaptive behaviour (+5.62) scores were significantly higher in MF than SF (95% CIs 0.03 to 6.79 and 1.78 to 9.38; p=0.048 and 0.004, respectively). Mean cognitive (+2.86, 95% CIs -1.10 to 6.80, p=0.08), language (+0.39, 95% CIs -2.53 to 3.30, p=0.87) and motor (+0.90, 95% CIs -2.32 to 4.13, p=0.49) scores tended to be higher in MF than SF, but the differences between the two groups were not significant. BFR scored higher on Bayley-III than either MF or SF at 6 and 12 months. Cognitive scores were significantly higher in BFR than SF (95% CI 0.05 to 7.20; p=0.045), but not MF (p=0.74) at 6 months. Short-term memory was significantly higher in MF than SF at 12 months (95% CI 1.40 to 12.33; p=0.002). At 4 months, serum gangliosides were significantly higher in MF and BFR than SF (95% CI 0.64 to 13.02; p=0.025). Milk intake, linear growth, body mass and head circumference were not significantly different between formula-fed groups. MFGM supplementation in early life supports adequate growth, increased serum gangliosides concentration and improves some measures of cognitive development in Chinese infants.

Micronutrient and Glucose-Related Biomarkers Until 24 Mo of Age in Infants Receiving Formula With Added Bovine Milk Fat Globule Membrane Through the First Year of Life: An RCT

ObjectivesBovine milk fat globule membrane (bMFGM) added in routine infant formula supports normal growth and safety through 24 mo of age in term infants. The impact on micronutrients and glucose-related biomarkers is assessed here. MethodsIn this double-blind, randomized, controlled trial, formula-fed infants were enrolled (<120 days of age) and randomized to receive a standard cow’s milk-based infant formula (SF, n = 174) or a similar formula with added whey protein-lipid concentrate (5 g/L; bMFGM; EF n = 173); exclusively breastfed infants were enrolled as a reference (HM, n = 235). In 50% of infants (chosen at random), parents agreed to blood collection (2–4 h fasting) at baseline, 6, 12, and 24 mo of age. Serum micronutrients (zinc, iron, ferritin, transferrin receptor) and glucose-related biomarkers (glucose, insulin, HOMA-IR [Homeostatic Model Assessment-Insulin Resistance], IGF-1) were analyzed. ResultsAt baseline, significant differences in markers of iron status (serum iron, ferritin) and glucose-related biomarkers (glucose, HOMA-IR, and IGF-1) were detected between HM and study formula groups. At 6 and 12 mo, no differences in any measure were detected between study formula groups. Serum iron and ferritin at 12 mo as well as glucose-related biomarkers at 6 mo (insulin, HOMA-IR, IGF-1) and 12 mo (IGF-1 only) were lower in the HM vs study formula groups. By 24 mo, micronutrients and glucose-related biomarkers were similar between study formula groups (with the exception of significantly lower serum iron in the SF group); for HM vs study formula groups, differences included significantly lower zinc and IGF-1. ConclusionsPatterns of micronutrients and glucose-related biomarkers were similar through two years of age in infants who received formula through one year. This study add to the body of data available for glucose-related biomarkers in children at two years of age and younger. Funding SourcesThe study was funded by Mead Johnson Nutrition (MJN). TMP, SSW, and JLW are currently, and CLB was previously employed by MJN.

Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes: A randomized controlled trial.

BackgroundProteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants.ObjectiveTo compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants.DesignFF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively.ResultsCompared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups.ConclusionsContrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.