Systemic immune markers and infection risk in preterm infants fed human milk fortified with bovine colostrum or conventional fortifier, a secondary analysis of the FortiColos trial.

BACKGROUND: For very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC), rich in anti-inflammatory milk factors, is considered an alternative. We investigated if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants. METHODS: For a secondary analysis of a multicenter, randomized controlled trial (NCT03537365), very preterm infants (26-31 weeks gestation, 23% small for gestational age, SGA) were randomized to receive BC (ColoDan, Biofiber, Denmark, n = 113) or conventional fortifier (PreNAN, Nestlé, Switzerland, n = 116). Infection was defined as antibiotic treatment for five or more consecutive days and 29 cytokines/chemokines were measured in plasma before and after start of fortification. RESULTS: In general, infection risk after start of fortification was associated with low gestational age, SGA status and antibiotics use prior to fortification. Adjusted for confounders, infants fortified with BC showed more infection episodes (20 vs 12%, P < 0.05) and higher cumulative infection risk (hazard ratio, HR 1.9, P = 0.06), particularly for SGA infants (HR 3.6, P < 0.05). Additionally, BC-fortified infants had higher levels of TH2-related cytokines/chemokines (IL-10, MDC, MCP4) and reduced levels of cytokines related to TH1/TH17-responses (IL-15, IL-17, GM-CSF). The differences were most pronounced in SGA infants, displaying higher levels of TH2-related IL-4, IL-6, and IL-13, and lower interferon-γ and IL-1α levels in the BC group. CONCLUSION: Infants fortified with BC displayed a delayed shift from TH2- to TH1-biased systemic immunity, notably in SGA infants, possibly influenced by multiple confounding factors, alongside elevated antibiotic use, suggesting increased susceptibility to infection.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Bovine Colostrum in Increased Intestinal Permeability in Healthy Athletes and Patients: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Increasing intestinal permeability causes chronic inflammation, which is one of the etiological factors of many diseases that presently constitute global challenges. AIMS: Considering the importance of developing therapies to eliminate the increased intestinal permeability, in this systematic review and meta-analysis, we analyze the impact of bovine colostrum (BC) on the gut barrier and its permeability. METHODS: Online databases, including PubMed, ISI Web of Science, and Scopus, were searched to find pertinent articles up to March 2022. Weighted mean difference (WMD) and 95% confidence intervals (CI) were considered as effect sizes. The random-effects model was used to pool the study results. RESULTS: A total of ten articles were included in the meta-analysis. The pooled effect revealed a significant reduction in the 5-h urinary lactulose/rhamnose ratio after BC consumption [mean difference (MD): -0.24; 95% CI -0.43 to -0.04; I2 = 99%] and urinary lactulose/mannitol ratio (MD: -0.01; 95% CI -0.02 to -0.001; I2 = 29.8%). No differences were observed in the plasma intestinal fatty acid-binding protein (I-FABP) between BC and control groups (MD: 2.30; 95% CI -293.9 to 298.5; I2 = 92%). CONCLUSIONS: BC supplementation significantly reduced intestinal permeability; however, to confirm the results, more randomized clinical trials considering different quality, dose, and duration are needed.

Effects of parity, seasonal heat stress, and colostrum collection time postpartum on colostrum quality of Holstein cattle in an arid region.

The aim of this study was to determine effects of parity (primiparous vs. multiparous), seasonal heat stress at calving (summer vs. winter), and time postpartum on some parameters associated with colostrum quality in Holstein cows reared in the Sonoran Desert ecosystem. Forty-seven cows (11 primiparous and 36 multiparous) expected to calve during summer, and 46 cows during winter (14 primiparous and 32 multiparous) were randomly selected. Management and feeding before and after parturition were similar for cows in both seasons. After parturition, colostrum from all cows was evaluated for volume, weight, temperature, density, and content of fat, protein, solids non-fat (SNF), and immunoglobulins (IGG). Data were analyzed with a model that included effects of parity status, calving season, and time postpartum, as well as all interactions. Colostrum produced in summer was warmer (P < 0.01) by almost 6 °C than winter colostrum, while colostrum from multiparous was warmer (P = 0.02) by 1.2 °C than that produced by primiparous cows. Colostrum volume and weight were not impacted by parity, calving season or time postpartum. Density, protein, and SNF content in colostrum were higher (P < 0.01) in multiparous vs. primiparous cows, as well as at parturition (0 h postpartum) than at 12 h postpartum (P < 0.01). At calving (0 h), spring colostrum had higher fat content (P < 0.01) and lower (P < 0.01) IGG concentration than that collected in summer, and no difference (P > 0.05) between seasons was observed for these components at 12 h postpartum. Multiparous cows produced colostrum with higher (P < 0.01) IGG concentrations than primiparous cows. In conclusion, only 0-h colostrum and that from multiparous cows was categorized as "Excellent," meanwhile the colostrum produced under summer heat stress was characterized as "Good" with reduced fat content. While the lacteal secretion collected at 12 post-partum still classified as colostrum, substantially lower contents of IGG, protein, fat, and SNF decreased its classification to "Poor" from the classification of "Excellent" at 0 h postpartum.

Key changes in bovine milk immunoglobulin G during lactation: NeuAc sialylation is a hallmark of colostrum immunoglobulin G N-glycosylation.

We monitored longitudinal changes in bovine milk IgG in samples from four cows at 9 time points in between 0.5 and 28 days following calving. We used peptide-centric LC-MS/MS on proteolytic digests of whole bovine milk, resulting in the combined identification of 212 individual bovine milk protein sequences, with IgG making up >50 percent of the protein content of every 0.5 d colostrum sample, which reduced to ≤3 percent in mature milk. In parallel, we analyzed IgG captured from the bovine milk samples to characterize its N-glycosylation, using dedicated methods for bottom-up glycoproteomics employing product ion-triggered hybrid fragmentation; data are available via ProteomeXchange with identifier PXD037755. The bovine milk IgG N-glycosylation profile was revealed to be very heterogeneous, consisting of >40 glycoforms. Furthermore, these N-glycosylation profiles changed substantially over the period of lactation, but consistently across the four individual cows. We identified NeuAc sialylation as the key abundant characteristic of bovine colostrum IgG, significantly decreasing in the first days of lactation, and barely detectable in mature bovine milk IgG. We also report, for the first time to our knowledge, the identification of subtype IgG3 in bovine milk, alongside the better-documented IgG1 and IgG2. The detailed molecular characteristics we describe of the bovine milk IgG, and their dynamic changes during lactation, are important not only for the fundamental understanding of the calf's immune development, but also for understanding bovine milk and its bioactive components in the context of human nutrition.

Preparative separation of immunoglobulins from bovine colostrum by continuous divergent-flow electrophoresis.

Immunoglobulins in bovine colostrum were separated and fractionated from other proteins using the method and instrumentation developed in our laboratory. The proposed separation was based on bidirectional isotachophoresis/moving boundary electrophoresis with electrofocusing of the analytes in a pH gradient from 3.9 to 10.1. The preparative instrumentation included the trapezoidal non-woven fabric that served as separation space with divergent continuous flow. The defatted and casein precipitate-free colostrum supernatant was loaded directly into the instrument without any additional colostrum pre-preparation. Immunoglobulin G was fractionated from other immune proteins such as bovine serum albumin, ß-lactoglobulin, and α-lactalbumin, and was continuously collected in separated fractions over 3 h. The fractions were further processed, and isolated immunoglobulin G in the liquid fractions was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by re-focusing in gel isoelectric focusing. Separated immunoglobulin G was detected in seven fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a gradually decreased concentration in the fractions. Re-focusing of the proteins in the fractions by gel isoelectric focusing revealed multiple separated zones of immunoglobulin G with the isoelectric point values covering the range from 5.4 to 7.2. Each fraction contained distinct zones with gradually increased isoelectric point values and decreased concentrations from fraction to fraction.

Influence of lactic acid fermentation on the microbiological parameters, biogenic amines, and volatile compounds of bovine colostrum.

In this study we hypothesized that the relations between the bovine colostrum (BC) microbiota, biogenic amine (BA) as well as volatile compound (VC) profiles can lead to new deeper insights concerning the BC changes during the biological preservation. To implement such an aim, BC samples were collected from 5 farms located in Lithuania and fermented with Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains. Nonfermented and fermented BC were subjected to microbiological [lactic acid bacteria (LAB), Escherichia coli, and total bacteria (TBC), total Enterobacteriaceae (TEC) and total mold and yeast (M-Y) viable counts] and physicochemical (pH, color coordinates, BA content and VC profile) parameters evaluation, and the relationship between the tested parameters were also further analyzed. In comparison pH and dry matter (DM) of nonfermented samples, significant differences were not found, and pH of BC was, on average, 6.30, and DM, on average, 27.5%. The pH of fermented samples decreased, on average, until 4.40 in Lp. plantarum fermented group, and, on average, until 4.37 in Lc. paracasei fermented group. Comparing color characteristics among nonfermented BC groups, significant differences between lightness (L*) and yellowness (b*) were not detected, however, the origin (i.e., agricultural company), LAB strain used for fermentation and the interaction between these factors were statistically significant on BC redness (a*) coordinate. The microbial contamination among all the tested BC groups was similar. However, different LAB strains used for BC fermentation showed different effects toward the microbial contamination reduction, and specifically Lc. paracasei was more effective than Lp. plantarum strain. Predominant BA in BC were putrescine and cadaverine. The main VC in nonfermented and fermented BC were decane, 2-ethyl-1-hexanol, dodecane, 1,3-di-tert-butylbenzene, 3,6-dimethyldecane and tetradecane. Moreover, this study showed worrying trends with respect to the frozen colostrum storage, because most of the dominant VC in BC were contaminants from the packaging material. Additionally, significant correlations between separate VC and microbial contamination were obtained. Finally, these experimental results showed that the separate VC in BC can be an important marker for biological as well as chemical contamination of BC. Also, it should be pointed out that despite the fermentation with LAB is usually described as a safe and natural process with many advantages, control of BA in the end product is necessary.

The effect of maternal supply of rumen-protected protein to Holstein Friesian cows during the dry period on the transfer of passive immunity and colostral microbial composition.

The objective of this study was to analyze if maternal supply of rumen-protected protein during the dry period can affect the IgG concentration and microbial composition of colostrum and the IgG absorption and fecal microbial composition in the calf. Seventy-four multiparous Holstein Friesian (HF) dairy cows were stratified per parity and randomly assigned to one of 2 different dry period diets, a diet with a low crude protein (CP) level (LP) and a diet with a high CP level (HP) by addition of rumen-undegraded protein (RUP; formaldehyde-treated soybean meal, Mervobest, Nuscience, Drongen, Belgium). Colostrum was collected within 1 h after calving and IgG concentration was quantified by radial immunodiffusion analysis. Forty-nine calves (23 female and 26 male) were enrolled in the trial with a 2 × 2 factorial design, with prenatal and postnatal treatment as the 2 independent variables. This led to 4 experimental groups: LPLP, LPHP, HPLP, and HPHP, in which the first 2 letters refer to the prenatal treatment (diet of the dam) and the last 2 refer to the postnatal treatment (diet of the colostrum-producing cow). Calves received 3× 2 L of colostrum within 2, 6, and 24 h after birth. Meconium and feces were collected solely from female calves (n = 18) by digital palpation of the rectum, immediately after birth and before colostrum administration and at d 3 of age. Microbial DNA was extracted from meconium (n = 9), feces (n = 15), and colostrum (n = 49). Amplicon sequencing of the bacterial V3-V4 region of the 16S rRNA gene was performed for characterization of the bacterial communities. Colostrum IgG concentration was higher in cows that were supplemented with RUP, especially in cows entering their second lactation (LSM ± SEM 61.3 ± 2.3 vs. 55.2 ± 2.8 g of IgG/L). Calves born out of LP cows that received colostrum from HP cows (LPHP) had a lower serum IgG level compared with HPHP and LPLP calves (LSM ± SEM 14.2 ± 1.3 vs. 18.8 ± 1.2 and 20.9 ± 1.3 g of IgG/L in HPHP and LPLP, respectively). The most abundant phyla in colostrum were Proteobacteria (48.2%), Firmicutes (24.8%), Bacteroidetes (9.5%), and Actinobacteria (5.0%). The most abundant phyla in calf meconium and feces were Firmicutes (42.5 and 47.5%), Proteobacteria (21.7% and 33.7%), Bacteroidetes (16.8% and 15.7%), and Actinobacteria (2.9% and 3.1%). There was no difference in the overall microbial communities between colostrum from HP and LP cows. However, 2 genera (both members of the family Lachnospiraceae) were more abundant in colostrum from HP cows compared with LP cows. The microbial composition of meconium, feces and colostrum differed from each other. Fecal samples were more similar to each other and are characterized by a lower intersample diversity compared with colostrum and meconium samples. To conclude, increasing the CP level by addition of RUP in the dry period diet affected the colostrum IgG concentration and the transfer of passive immunity, but did not change the overall microbial composition of colostrum nor of meconium and feces in the calf.

Immunomodulatory Effects of Modified Bovine Colostrum, Whey, and Their Combination with Other Natural Products: Effects on Human Peripheral Blood Mononuclear Cells.

Background: Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood. Objectives: This study evaluated the influence of bovine colostrum products, a whey product, or their combinations with other natural products on human peripheral blood mononuclear cells' (PBMC) ability to produce cytokines upon activation. Methods: PBMCs were pretreated with ultrafiltered colostrum, nano-filtered bovine colostrum, egg yolk extract, a botanical blend, colostrum + egg yolk extract, colostrum + egg yolk + botanical blend, and fermented whey and then stimulated with lipopolysaccharide or phytohemagglutinin. Cytokine production was measured by the Luminex assay. Results: All study products demonstrated immunomodulatory properties by regulating cytokines production by activated PBMCs. Ultrafiltered colostrum alone displayed the highest immune stimulatory activity. It stimulated proinflammatory cytokine production by lipopolysaccharide-activated PBMCs and suppressed cytokine production by phytohemagglutinin-activated cells. Other study products mainly suppressed cytokine release by both cell types. The immunomodulatory properties depended upon the dose of the products used in the study. Conclusions: All tested products modulated innate and adaptive immune cell activities. Most of the products demonstrated anti-inflammatory properties, except ultrafiltered colostrum, which stimulated the lipopolysaccharide-activated PBMC production of inflammatory cytokines. These products can be potentially used to support overall immune health.

Effect of topical bovine colostrum in wound healing of corneal surface after acute ocular alkali burn in mice.

The purpose of this study was to evaluate the effect of bovine colostrum (BC) in the regeneration of corneal epithelial cells on an ocular alkali burn model. Twenty-four C57BL/6 mice were categorized into two gender/age-matched groups for treatment. Two days after inducing a corneal alkali burn in all left eyes with 4 µl of sodium hydroxide 0.15 mol/l, both eyes of group 1 were treated with BC 4 times per day, and both eyes of group 2 were treated with isotonic saline solution (SS). The epithelial defect was photographed and measured by fluorescein staining on days two, four, seven, and ten. Ocular burn damage was assessed with a pre-established classification in clock hours from the limbus. After 10 days both eyes were processed, half of the group's corneas were assessed histopathologically, and the other half was used for pro/anti-inflammatory cytokine quantification using ELISA. BC treated (Group 1) corneas revealed significantly improved fluorescein staining score for limbal involvement when compared to SS treated (Group 2) corneas at days 4 (p = 0.013), 7 (p < 0.001), and 10 (p < 0.001), respectively. No differences were noted in limbal involvement at day 2 between the two groups (p > 0.99). The overall change (difference in slope) in fluorescein staining for limbal involvement between days 2 and 10 was -0.1669 (p = 0.006). Histologic examinations and cytokine measurements of group 2 demonstrated a strong inflammatory component compared to group 1. Our data indicates that topical application of BC facilitates corneal re-epithelialization and wound healing by suppressing the inflammatory process in an ocular alkali burn model.

Exploring the microbial composition of Holstein Friesian and Belgian Blue colostrum in relation to the transfer of passive immunity.

For centuries, multicellular organisms have lived in symbiosis with microorganisms. The interaction with microorganisms has been shown to be very beneficial for humans and animals. During a natural birth, the initial inoculation with bacteria occurs when the neonate passes through the birth canal. Colostrum and milk intake are associated with the acquisition of a healthy gut flora. However, little is known about the microbial composition of bovine colostrum and the possible beneficial effects for the neonatal calf. In this prospective cohort study, the microbial composition of first-milking colostrum was analyzed in 62 Holstein Friesian (HF) and 46 Belgian Blue (BB) cows by performing amplicon sequencing of the bacterial V3-V4 region of the 16S rRNA gene. Calves received, 3 times, 2 L of their dam's colostrum within 24 h after birth. Associations between colostral microbial composition and its IgG concentration, as well as each calf's serum IgG levels, were analyzed. Colostrum samples were dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The 10 most abundant genera in the complete data set were Acinetobacter (16.2%), Pseudomonas (15.1%), a genus belonging to the Enterobacteriaceae family (4.9%), Lactococcus (4.0%), Chryseobacterium (3.9%), Staphylococcus (3.6%), Proteus (1.9%), Streptococcus (1.8%), Enterococcus (1.7%), and Enhydrobacter (1.5%). The remaining genera (other than these top 10) accounted for 36.5% of the counts, and another 8.7% were unidentified. Bacterial diversity differed significantly between HF and BB samples. Within each breed, several genera were found to be differentially abundant between colostrum of different quality. Moreover, in HF, the bacterial composition of colostrum leading to low serum IgG levels in the calf differed from that of colostrum leading to high serum IgG levels. Results of the present study indicate that the microbes present in colostrum are associated with transfer of passive immunity in neonatal calves.

Bovine Colostrum Treatment of Specific Cancer Types: Current Evidence and Future Opportunities.

Worldwide, the incidence of cancer is on the rise. Current cancer treatments include chemotherapy, radiation therapy, and surgery. Chemotherapy and radiation treatment are typically associated with severe adverse effects and a decline in patients' quality of life. Anti-cancer substances derived from plants and animals need to be evaluated therapeutically as it is cost-effective, have fewer side effects, and can improve cancer patients' quality of life. Recently, bovine colostrum (BC) has attracted the interest of numerous researchers investigating its anti-cancer potential in humans. Dressings loaded with BC are beneficial in treating chronic wounds and diabetic foot ulcers. Lactoferrin, a glycoprotein with potent anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial effects, is abundant in BC. The BC pills successfully promote the regression of low-grade cervical intraepithelial neoplasia when administered intravaginally. The biological, genetic, and molecular mechanisms driving BC remain to be determined. Oral BC supplements are generally well-tolerated, but some flatulence and nausea may happen. To evaluate the therapeutic effects, long-term safety, and appropriate dosages of BC drugs, well-designed clinical trials are necessary. The purpose of this article is to emphasize the anti-cancer potential of BC and its constituents.

Qualitative identification of mature milk adulteration in bovine colostrum using noise-reduced dielectric spectra and linear model.

BACKGROUND: The rapid and accurate identification of colostrum, a strong non-homogeneous food, remains a challenge. In the present study, the dielectric spectra including the dielectric constant (ε') and loss factor (ε″) of 154 colostrum samples adulterated with 0-50% mature milk were measured from 20 to 4500 MHz. RESULTS: The results showed that the noise-reducing spectral preprocessing, including Savitzky-Golay (S-G), second derivative (SD), and S-G + SD, was significantly better than scattering-eliminating, including standard normal variate (SNV), multiplicative scatter correction (MSC), and SNV + MSC. The combination of S-G and SD was the best. Principal component analysis results demonstrated that dielectric spectroscopy is less susceptible to the inhomogeneity of colostrum and can be used to identify doped colostrum. The identification performance of linear models was better than that of non-linear models. The established linear discriminant analysis model based on full spectra had the best accuracy rates of 99.14% and 97.37% in the calibration and validation sets, respectively. Confirmatory tests on samples from different sources confirmed the satisfactory robustness of the proposed model. CONCLUSION: We found that the main unfavorable effect on the identification based on dielectric spectroscopy was noise interference, rather than scattering effect caused by inhomogeneity of colostrum. The satisfactory results undoubtedly cast light on rapid detection of strongly non-homogeneous foods based on dielectric spectroscopy. © 2022 Society of Chemical Industry.

Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life.

The newborn gut undergoes rapid colonization by commensal microorganisms and possible exposure to pathogens. The contribution of colostrum intake to host protection is well known; however, limited research exists on the intestinal innate immunity corresponding to colostrum intake during the passive immune transfer period in newborn ruminants. The aim of this study was to investigate the changes in bacterial community and expression of genes encoding toll-like receptors (TLR), mucins (MUC), antimicrobial peptides, and tight junctions in the jejunum of lambs that were fed colostrum during the first 24 h of life. Twenty-seven newborn lambs were used in this study, of which 18 lambs were bottle-fed pooled bovine colostrum within the first 2 h after birth to obtain an intake of approximately 8% of body weight. Lambs were slaughtered at 12 (n = 9) and 24 h (n = 9) after birth. The remaining 9 lambs without any feeding were slaughtered at 30 min after birth (0 h). Tissue and ligated segment samples from the jejunum were collected immediately after the lambs were slaughtered. The bacterial profile in the ligated jejunum segment was assessed using amplicon sequencing. The gene expression in the jejunum tissue was determined using quantitative real-time PCR. The relative abundances of Escherichia-Shigella, Lactobacillus, Lactococcus, and Streptococcus increased, whereas those of Sphingomonas, Phyllobacterium, Bradyrhizobium, and Rudaea decreased during the first 24 h of life. Expression of TLR2 and ß-defensin 109-like was upregulated at 12 h after birth, but a recovery was detected at 24 h; TLR3, TLR5, LYZ, MUC1, MUC13, MUC20, and CLDN7 showed a higher expression level in samples taken at 24 h than in those taken at 0 h. In addition, expression level of CLDN1, CLDN4, and the junctional adhesion molecule-1 tended to be higher at 24 h than at 0 h after birth. Correlation analysis indicated that TLR2 expression was negatively correlated with the relative abundance of Lactobacillus and Bradyrhizobium, whereas TLR5 expression was positively correlated with the relative abundance of Escherichia-Shigella and Pelagibacterium. These results suggest that TLR, MUC, antimicrobial peptides, and CLDN act together and play an important role in intestinal defense during the passive immune transfer period. They are potentially associated with microbial colonization. The findings from this study provide novel information to elucidate the role of colostrum components in regulating the development of the intestinal mucosal immune barrier in newborn lambs during the passive immune transfer period.

Evaluation of colostrum bioactive protein transfer and blood metabolic traits in neonatal lambs in the first 24 hours of life.

Colostrum is a unique resource that contributes to the passive transfer of immunity and plays a central role in the health status of neonatal ruminants. However, digestion and absorption of colostral proteins in the gut remain incompletely understood. Therefore, this study aimed to investigate the effect of bovine colostrum feeding on blood metabolic traits and to quantify colostral bioactive proteins in the gastrointestinal digesta and blood to evaluate intestinal transfer in neonatal lambs in the first 24 h of life. Fifty-four newborn lambs were used in this study, including 27 lambs fed pooled bovine colostrum and slaughtered at 6 (C6h), 12 (C12h), or 24 h (C24h) after birth; 18 lambs not fed any colostrum or milk and slaughtered at birth (N0h) or 24 h (N24h) after birth; and 9 milk-fed lambs slaughtered at 24 h (M24h) after birth. Lambs receiving colostrum or milk were bottle-fed within the first 2 h to obtain intakes of 8% of body weight at birth. Samples of blood and digesta from the abomasum, jejunum, and ileum were collected after slaughter. Serum concentrations of glucose, insulin, total protein, and aspartate aminotransferase were higher in colostrum-fed lambs than in N0h lambs. Serum concentrations of insulin, total protein, insulin-like growth factor 1, and γ-glutamyl transpeptidase were higher in C24h lambs than in N24h or M24h lambs. Apparent efficiencies of IgG absorption in C6h, C12h, and C24h lambs were 14.4, 26.8, and 17.2%, respectively, whereas apparent efficiencies of lactoferrin (LF), α-lactalbumin (α-LA), and ß-lactoglobulin (ß-LG) absorption were very low in colostrum-fed lambs, with mean values of 0.06, 0.002, and 0.003%, respectively. Concentrations of IgG, LF, α-LA, and ß-LG in the digesta of the abomasum, jejunum, and ileum rapidly decreased from C6h to C24h lambs, and the disappearance rates of IgG, LF, α-LA, and ß-LG were higher in lambs from C6h to C12h (62.1, 75.7, 91.3, and 95.0% for IgG, LF, α-LA, and ß-LG, respectively) than from C12h to C24h (34.6, 22.5, 7.5, and 2.2% for IgG, LF, α-LA, and ß-LG, respectively). These results indicated that bovine colostrum feeding improved the metabolic and immunological status of lambs, and that ingested colostral IgG was prone to intact uptake into the blood, whereas almost all ingested LF, α-LA, and ß-LG disappeared in the lumen of the gastrointestinal tract in a time-dependent manner. The findings provide novel information for exploring selective absorption of colostral compounds in the small intestine of lambs.

Quantitative analysis of differentially expressed milk fat globule membrane proteins between donkey and bovine colostrum based on high-performance liquid chromatography with tandem mass spectrometry proteomics.

This study was designed to provide novel insights into milk fat globule membrane (MFGM) proteins in donkey colostrum (DC) and bovine colostrum (BC) using quantitative proteomics. In total, 179 (DC) and 195 (BC) MFGM proteins were characterized, including 71 shared, 108 DC-specific, and 124 BC-specific proteins. Fifty-one shared proteins were selected as differentially expressed MFGM proteins, including 21 upregulated and 30 downregulated proteins in DC. Gene ontology analysis showed that these proteins were mainly enriched in cellular components, including the extracellular exosome, extracellular space, and plasma membrane. Additionally, they were further involved in metabolic pathways, including cholesterol metabolism, the peroxisome proliferator-activated receptor signaling pathway, and purine metabolism. Furthermore, several key protein factors with high connectivity were identified via protein-protein interaction analysis. These results provide more comprehensive knowledge of differences in the biological properties of MFGM proteins in DC and BC as well as pave the way for future studies of the nutritional and functional requirements of these important ingredients toward the development of dairy products based on multiple milk sources.

Preservation of protective capacity of hyperimmune anti-Stx2 bovine colostrum against enterohemorrhagic Escherichia coli O157:H7 pathogenicity after pasteurization and spray-drying processes.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a major etiologic agent that causes bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the main virulence factor of EHEC responsible for the progression to HUS. Although many laboratories have made efforts to develop an effective treatment for Stx-mediated HUS, a specific therapy has not been found yet. Human consumption of bovine colostrum is known to have therapeutic effects against several gastrointestinal infections because of the peptide and proteins (including antibodies) with direct antimicrobial and endotoxin-neutralizing effects contained in this fluid. We have previously demonstrated that colostrum from Stx type 2 (Stx2)-immunized pregnant cows effectively prevents Stx2 cytotoxicity and EHEC O157:H7 pathogenicity. In this study we evaluated the preservation of the protective properties of hyperimmune colostrum against Stx2 (HIC-Stx2) after pasteurization and spray-drying processes by performing in vitro and in vivo assays. Our results showed that reconstituted HIC-Stx2 colostrum after pasteurization at 60°C for 60 min and spray-dried under optimized conditions preserved specific IgG that successfully neutralized Stx2 cytotoxicity on Vero cells. Furthermore, this pasteurized/dehydrated and reconstituted HIC-Stx2 preserved the protective capacity against EHEC infection in a weaned mice model. The consumption of hyperimmune HIC-Stx2 bovine colostrum could be effective for HUS prevention in humans as well as in EHEC control in calves. However, further studies need to be done to consider its use for controlling EHEC infections.

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0-700 µM). Colostrum co-treated with DEX was executed at 0.1-5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

Using BAMLET complex in a functional spreadable cheese elaborated with bovine colostrum.

BAMLET is a bioactive complex formed by the interaction between α-Lactoalbumin (α-LA) and oleic acid which exhibits cytotoxic activity against cancer cells. BAMLET is selectively cytotoxic to malignant cells while sparing the healthy ones. There are, however, no reports about its application in a food matrix. The objective of this work was to synthetize the BAMLET complex from oleic acid and bovine colostrum from the second and third milkings which naturally contain α-LA to prepare two functional spreadable cheeses. The complex was successfully formed and retained in the cheeses as verified through SDS-PAGE applied to the whey obtained. The spreadable cheese from the second milking had a higher protein content (13.56 ± 0.02%) and a higher yield (40%) than the product obtained from the third milking. Even though the cheeses did not show any significant differences (p > 0.05) in the inhibition of the angiotensin-converting enzyme 1, their inhibitory activities were good, as a 0.5 g portion of the cheese from the second milking was sufficient to inhibit 57.52 ± 9.17%, while the cheese from the third milking inhibited 51.48 ± 1.07% of the enzyme. The sensory analysis showed a good acceptance for both spreadable cheeses.

Nutrient Restriction has Limited Short-Term Effects on Gut, Immunity, and Brain Development in Preterm Pigs.

BACKGROUND: Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term. OBJECTIVE: Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth. METHODS: Forty-four preterm caesarean-delivered pigs (Danish Landrace × Large White × Duroc, birth weight 975 ± 235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg·d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group). RESULTS: The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected. CONCLUSION: Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.