scholarly journals Raw Cow’s Milk Reduces Allergic Symptoms in a Murine Model for Food Allergy—A Potential Role For Epigenetic Modifications

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1721 ◽  
Author(s):  
Abbring ◽  
Wolf ◽  
Ayechu-Muruzabal ◽  
Diks ◽  
Alhamdan ◽  
...  
Keyword(s):  
T Cells ◽  
Food Allergy ◽  
T Cell ◽  
Histone Acetylation ◽  
Murine Model ◽  
Raw Milk ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
Allergic Symptoms ◽  
Raw Cow’S Milk

Epidemiological studies identified raw cow’s milk consumption as an important environmental exposure that prevents allergic diseases. In the present study, we investigated whether raw cow’s milk has the capacity to induce tolerance to an unrelated, non-milk, food allergen. Histone acetylation of T cell genes was investigated to assess potential epigenetic regulation. Female C3H/HeOuJ mice were sensitized and challenged to ovalbumin. Prior to sensitization, the mice were treated with raw milk, processed milk, or phosphate-buffered saline for eight days. Allergic symptoms were assessed after challenge and histone modifications in T cell-related genes of splenocyte-derived CD4+ T cells and the mesenteric lymph nodes were analyzed after milk exposure and after challenge. Unlike processed milk, raw milk decreased allergic symptoms. After raw milk exposure, histone acetylation of Th1-, Th2-, and regulatory T cell-related genes of splenocyte-derived CD4+ T cells was higher than after processed milk exposure. After allergy induction, this general immune stimulation was resolved and histone acetylation of Th2 genes was lower when compared to processed milk. Raw milk reduces allergic symptoms to an unrelated, non-milk, food allergen in a murine model for food allergy. The activation of T cell-related genes could be responsible for the observed tolerance induction, which suggested that epigenetic modifications contribute to the allergy-protective effect of raw milk.

scholarly journals Suppression of Food Allergic Symptoms by Raw Cow’s Milk in Mice is Retained after Skimming but Abolished after Heating the Milk—A Promising Contribution of Alkaline Phosphatase

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1499 ◽  
Author(s):  
Suzanne Abbring ◽  
Joseph Thomas Ryan ◽  
Mara A.P. Diks ◽  
Gert Hols ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Protective Effect ◽  
Raw Milk ◽  
Fat Content ◽  
Cow’S Milk ◽  
Protective Effects ◽  
Pasteurized Milk ◽  
Cow's Milk ◽  
Allergic Symptoms ◽  
Raw Cow’S Milk

Raw cow’s milk was previously shown to suppress allergic symptoms in a murine model for food allergy. In the present study, we investigated the contribution of fat content and heat-sensitive milk components to this allergy-protective effect. In addition, we determined the potency of alkaline phosphatase (ALP), a heat-sensitive raw milk component, to affect the allergic response. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk spiked with ALP, or phosphate-buffered saline for eight days prior to sensitization and challenge with ovalbumin (OVA). Effects of these milk types on the allergic response were subsequently assessed. Similar to raw milk, skimmed raw milk suppressed food allergic symptoms, demonstrated by a reduced acute allergic skin response and low levels of OVA-specific IgE and Th2-related cytokines. This protective effect was accompanied by an induction of CD103+CD11b+ dendritic cells and TGF-β-producing regulatory T cells in the mesenteric lymph nodes. Pasteurized milk was not protective but adding ALP restored the allergy-protective effect. Not the fat content, but the heat-sensitive components are responsible for the allergy-protective effects of raw cow’s milk. Adding ALP to heat-treated milk might be an interesting alternative to raw cow’s milk consumption, as spiking pasteurized milk with ALP restored the protective effects.

scholarly journals Raw Milk-Induced Protection against Food Allergic Symptoms in Mice Is Accompanied by Shifts in Microbial Community Structure

2021 ◽  
Vol 22 (7) ◽  
pp. 3417
Author(s):  
Suzanne Abbring ◽  
Phillip A. Engen ◽  
Ankur Naqib ◽  
Stefan J. Green ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Microbial Community ◽  
Relative Abundance ◽  
Allergic Sensitization ◽  
Raw Milk ◽  
Cow’S Milk ◽  
Protective Effects ◽  
Pasteurized Milk ◽  
Cow's Milk ◽  
Allergic Symptoms ◽  
Raw Cow’S Milk

The mechanism underlying the allergy-protective effects of raw cow’s milk is still unknown, but the modulation of the gut microbiome may play a role. The effects of consuming raw cow’s milk or processed milk on fecal microbial communities were therefore characterized in an experimental murine model. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk supplemented with alkaline phosphatase (ALP), or phosphate-buffered saline (PBS) for eight days prior to sensitization and challenge with ovalbumin (OVA). Fecal samples were collected after milk exposure and after OVA sensitization, and microbiomes were characterized using 16S ribosomal RNA gene amplicon sequencing. Treatment with raw milk prior to OVA sensitization increased the relative abundance of putative butyrate-producing bacteria from the taxa Lachnospiraceae UCG-001, Lachnospiraceae UCG-008, and Ruminiclostridium 5 (Clostridial clusters XIVa and IV), while it decreased the relative abundance of Proteobacterial genera such as Parasutterella, a putative pro-inflammatory bacterial genus. This effect was observed after eight days of raw milk exposure and became more pronounced five weeks later, after allergic sensitization in the absence of milk. Similar trends were observed after treatment with skimmed raw milk. Conversely, the feeding of pasteurized milk led to a loss of allergy protection and a putative dysbiotic microbiome. The addition of ALP to pasteurized milk restored the protective effect observed with raw milk and mitigated some of the microbial community alterations associated with milk pasteurization. Raw milk-induced protection against food allergic symptoms in mice is accompanied by an increased relative abundance of putative butyrate-producing Clostridiales and a decreased relative abundance of putative pro-inflammatory Proteobacteria. Given the safety concerns regarding raw milk consumption, this knowledge is key for the development of new, microbiologically safe, preventive strategies to reduce the incidence of allergic diseases.

Alteration of Allergen Fold of Bos d 5 into a Hypoallergenic Vaccine for Immunotherapy of Cow’s Milk Allergy

2021 ◽  
pp. 1-12
Author(s):  
Yaqiong Cui ◽  
Yang Yu ◽  
Shuxiang Lin ◽  
Li Xu ◽  
Liuxu Li ◽  
...  
Keyword(s):  
Food Allergy ◽  
T Cell ◽  
Cow’S Milk Allergy ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
T Cell Epitopes ◽  
Dot Blot ◽  
Allergen Specific Immunotherapy ◽  
Cow's Milk ◽  
Cow's Milk Allergy

<b><i>Background:</i></b> Cow’s milk allergy (CMA) is the most common IgE-mediated food allergy and Bos d 5 is the major allergen in cow’s milk proteins. More than 60% of the patients with CMA are sensitized to this protein. <b><i>Methods and Results:</i></b> A recombinant protein, encoded by a synthetic gene and consisting of reassembled Bos d 5 fragments, was expressed in <i>E. coli</i> strain BL21 (DE3) cells and purified to homogeneity. The B5M lacked relevant IgE-reactivity and allergenic activity compared with Bos d 5 in dot-blot and basophil activation assays. T-cell proliferation experiments demonstrated that B5M preserved the main T cell epitopes of Bos d 5. Immunization of rabbits with B5M induced protective IgG antibodies that blocked the binding of patients’ IgE antibodies to the wild-type allergen and inhibited the degranulation of basophils induced by Bos d 5. <b><i>Conclusion:</i></b> Thus, we developed a new strategy, which was based on rational molecular reassembly for allergen-specific immunotherapy (AIT) of CMA and food allergy.

scholarly journals Direct Inhibition of the Allergic Effector Response by Raw Cow’s Milk—An Extensive In Vitro Assessment

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1258
Author(s):  
Suzanne Abbring ◽  
Bart R. J. Blokhuis ◽  
Julie L. Miltenburg ◽  
Kiri G. J. Romano Olmedo ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Allergic Diseases ◽  
Raw Milk ◽  
Mast Cell Activation ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
Ige Mediated ◽  
Raw Cow’S Milk

The mechanisms underlying the allergy-protective effects of raw cow’s milk are poorly understood. The current focus is mainly on the modulation of T cell responses. In the present study, we investigated whether raw cow’s milk can also directly inhibit mast cells, the key effector cells in IgE-mediated allergic responses. Primary murine bone marrow-derived mast cells (BMMC) and peritoneal mast cells (PMC), were incubated with raw milk, heated raw milk, or shop milk, prior to IgE-mediated activation. The effects on mast cell activation and underlying signaling events were assessed. Raw milk was furthermore fractionated based on molecular size and obtained fractions were tested for their capacity to reduce IgE-mediated mast cell activation. Coincubation of BMMC and PMC with raw milk prior to activation reduced β-hexosaminidase release and IL-6 and IL-13 production, while heated raw milk or shop milk had no effect. The reduced mast cell activation coincided with a reduced intracellular calcium influx. In addition, SYK and ERK phosphorylation levels, both downstream signaling events of the FcεRI, were lower in raw milk-treated BMMC compared to control BMMC, although differences did not reach full significance. Raw milk-treated BMMC furthermore retained membrane-bound IgE expression after allergen stimulation. Raw milk fractionation showed that the heat-sensitive raw milk components responsible for the reduced mast cell activation are likely to have a molecular weight of > 37 kDa. The present study demonstrates that raw cow’s milk can also directly affect mast cell activation. These results extend the current knowledge on mechanisms via which raw cow’s milk prevents allergic diseases, which is crucial for the development of new, microbiologically safe, nutritional strategies to reduce allergic diseases.

scholarly journals Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3193
Author(s):  
Bilal Alashkar Alhamwe ◽  
Laura A. P. M. Meulenbroek ◽  
Désirée H. Veening-Griffioen ◽  
Tjalling M. D. Wehkamp ◽  
Fahd Alhamdan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Allergy ◽  
Histone Acetylation ◽  
Specific Ige ◽  
Allergic Response ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
T Helper ◽  
Cow's Milk ◽  
Ige Mediated

Immunoglobulin E (IgE)-mediated allergy against cow’s milk protein fractions such as whey is one of the most common food-related allergic disorders of early childhood. Histone acetylation is an important epigenetic mechanism, shown to be involved in the pathogenesis of allergies. However, its role in food allergy remains unknown. IgE-mediated cow’s milk allergy was successfully induced in a mouse model, as demonstrated by acute allergic symptoms, whey-specific IgE in serum, and the activation of mast cells upon a challenge with whey protein. The elicited allergic response coincided with reduced percentages of regulatory T (Treg) and T helper 17 (Th17) cells, matching decreased levels of H3 and/or H4 histone acetylation at pivotal Treg and Th17 loci, an epigenetic status favoring lower gene expression. In addition, histone acetylation levels at the crucial T helper 1 (Th1) loci were decreased, most probably preceding the expected reduction in Th1 cells after inducing an allergic response. No changes were observed for T helper 2 cells. However, increased histone acetylation levels, promoting gene expression, were observed at the signal transducer and activator of transcription 6 (Stat6) gene, a proallergic B cell locus, which was in line with the presence of whey-specific IgE. In conclusion, the observed histone acetylation changes are pathobiologically in line with the successful induction of cow’s milk allergy, to which they might have also contributed mechanistically.

Longitudinal Analysis of the Microbiological Quality of Raw Cow's Milk Samples Collected from Three Small Family Dairy Farms in Mexico Over a 2-Year Period

2019 ◽  
Vol 82 (12) ◽  
pp. 2194-2200 ◽  
Author(s):  
DIANA RIOS-MUÑIZ ◽  
JORGE F. CERNA-CORTES ◽  
CATALINA LOPEZ-SAUCEDO ◽  
ERIKA ANGELES-MORALES ◽  
MIRIAM BOBADILLA-del VALLE ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Microbiological Quality ◽  
Dairy Farms ◽  
Raw Milk ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
E Coli ◽  
Milk Samples ◽  
Three Samples ◽  
Raw Cow’S Milk

ABSTRACT In Mexico, the total milk production that family dairy farms (FDF) contribute is ca. 35%, but this milk is not evaluated for microbiological quality. Forty percent of the milk and dairy products consumed by Mexicans is unpasteurized. In total, 24 raw cow's milk samples from three FDF (one sample per each season from each FDF for two sequent years) were characterized for the presence of food quality indicator organisms, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, and Mycobacterium spp., by standard procedures. Escherichia coli presence was also evaluated by a direct count method and diarrheagenic E. coli (DEC) by molecular methods. On the basis of Mexican guidelines for raw milk entering production, 42% of samples exceeded the aerobic mesophilic bacteria limits. A total of 83% raw milk samples were positive for total coliforms, 54% for fecal coliforms, and 46% for E. coli. Forty-three E. coli isolates were selected and characterized for the presence of 11 DEC loci; of theses, 40 isolates were negative for all DEC loci, and 3 isolates, all collected from the same sample, were Shiga toxin 2 (stx2) positive and O157 antigen negative, and one stx2 isolate was resistant to 6 of the 16 antibiotics tested. None of the 24 raw milk samples were positive for Salmonella enterica, L. monocytogenes, or staphylococcal enterotoxin. S. aureus was isolated from nine samples, of which only three samples harbored resistant isolates. From three samples, four nontuberculous mycobacterial isolates were recovered (Mycobacteroides chelonae, Mycobacteroides porcinum, and two Mycobacteroides abscessus). All four isolates produced biofilm and had sliding motility, and three isolates (M. porcinum and two M. abscessus) were resistant to the two antibiotics tested (clarithromycin and linezolid). FDF provide raw milk to a large proportion of the Mexican population, but its consumption could be harmful to health, emphasizing the need to implement national microbiological quality guidelines for raw milk intended for direct human consumption. HIGHLIGHTS

scholarly journals Isolation and Molecular Identification and Antimicrobial Susceptibility of Providencia spp. from Raw Cow’s Milk in Baghdad, Iraq

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Nagham Mohammed Ayyal Al‐Gburi
Keyword(s):  
Antimicrobial Susceptibility ◽  
Raw Milk ◽  
Diffusion Method ◽  
Cow’S Milk ◽  
Biochemical Tests ◽  
Street Vendors ◽  
Cow's Milk ◽  
Milk Samples ◽  
Biolog Gn ◽  
Raw Cow’S Milk

A total of sixty raw milk samples were collected from (street vendors and shops) from Baghdad city, Iraq. The samples were inoculated into peptone water and, then, subcultured onto McConkey agar and Blood agar. Identification of isolates was confirmed by microscopic examination, cultural characteristic, biochemical tests, Vitek (VITEK®2 system), and Biolog GN substrate reactions followed by 16S rRNA and specific genes sequencing. Of 60 raw cow’s milk samples, Providencia spp. were identified only in 4 samples (6.67%) and P. rettgeri was the most common, 2/4 (50%), followed by P. stuartii and P. vermicola, 1/4 (25%) . Antimicrobial susceptibility tests were conducted against ten antibiotics by the disc diffusion method. All Providencia isolates showed multidrug resistance (MDR), and the absolute resistant was 100% to tetracycline, erythromycin, and doxycycline and 50% against ampicillin\sulbactam and amoxicillin/clavulanic acid. They were highly susceptible (100%) to trimethoprim, imipenem, and chloramphenicol. These findings indicate that milk might be contaminated with Providencia spp. leading to transmission to humans causing poisoning, diarrhea, and other infections. This is the first study of isolated Providencia spp. from raw cow’s milk.

A high fat soy oil diet enhances allergic symptoms while fish oil prevents allergic sensitization to cow's milk protein in mice via induction of regulatory T-cells

2014 ◽  
Vol 2 (3) ◽  
pp. 87
Author(s):  
L.W.J. van den Elsen ◽  
E.C.A.M. van Esch ◽  
G.A. Hofman ◽  
J. Kant ◽  
B.J.M. van de Heijning ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Fish Oil ◽  
Milk Protein ◽  
Allergic Sensitization ◽  
Cow’S Milk ◽  
Soy Oil ◽  
High Fat ◽  
Cow's Milk ◽  
Allergic Symptoms
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