Goat Milk Allergy and a Potential Role for Goat Milk in Cow's Milk Allergy.

In many parts of the world, goat milk has been part of the human diet for millennia. Allergy to goat's milk, not associated with allergy to cow's milk, is a rare disorder, although some cases have been described. Goat milk proteins have substantial homology with cow's milk proteins and even show cross-reactivity; therefore, they are not advised as an alternative to cow's milk for infants with IgE-mediated cow's milk allergies. However, there are indications that, due to the composition of the goat milk proteins, goat milk proteins show lower allergenicity than cow's milk due to a lower αS1-casein content. For this reason, goat milk might be a better choice over cow's milk as a first source of protein when breastfeeding is not possible or after the breastfeeding period. Additionally, some studies show that goat milk could play a role in specific types of non-IgE-mediated cow milk allergy or even in the prevention of sensitization to cow's milk proteins. This review discusses a possible role of goat milk in non-IgE mediated allergy and the prevention or oral tolerance induction of milk allergy.

Impact of maternal Bifidobacterium breve M-16V and scGOS/lcFOS supplementation during pregnancy and lactation on the maternal immune system and milk composition.

Introduction: Maternal synbiotic supplementation during pregnancy and lactation can significantly influence the immune system. Prebiotics and probiotics have a positive impact on the immune system by preventing or ameliorating among others intestinal disorders. This study focused on the immunomodulatory effects of B. breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosachairdes (lcFOS), including systemic and mucosal compartments and milk composition. Methods: Lewis rats were orally administered with the synbiotic or vehicle during pregnancy (21 days) and lactation (21 days). At the weaning day, small intestine (SI), mammary gland (MG), adipose tissue, milk, mesenteric lymph nodes (MLN), salivary gland (SG), feces and cecal content were collected from the mothers. Results: The immunoglobulinome profile showed increased IgG2c in plasma and milk, as well as elevated sIgA in feces at weaning. The supplementation improved lipid metabolism through enhanced brown adipose tissue activity and reinforced the intestinal barrier by increasing the expression of Muc3, Cldn4, and Ocln. The higher production of short chain fatty acids in the cecum and increased Bifidobacterium counts suggest a potential positive impact on the gastrointestinal tract. Discussion: These findings indicate that maternal synbiotic supplementation during gestation and lactation improves their immunological status and improved milk composition.

A retrospective comparison of IgE-mediated cow's milk protein allergy management strategies in pediatric cohorts.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA. METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk. RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group. CONCLUSION: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

Development of a low allergenic product for patients with milk allergy and assessment of its specific IgE reactivity.

BACKGROUND: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked-cake/muffin, to develop indirect in-house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients' sera via western blotting (WB) and indirect in-house ELISA. METHOD: A low allergenic product named biscotti-twice baked-cake was developed, and the total protein concentration was determined. The protein content was studied by SDS-PAGE and proteomics. Milk-specific IgE (sIgE) binding assays were performed by WB and indirect in-house ELISA by using patients' sera. RESULTS: Casein band intensity was observed to be lower in the biscotti-twice baked-cake than in the once baked-cake (p = .014). Proteomics analysis and αS1-casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked-cake was shown by WB (p = .0012) and by indirect in-house ELISA (p = .0001). In the ROC analysis, the area under the curve (AUC) of the in-house ELISA IgE was comparable with Uni-CAP milk and casein sIgE. The AUC of the in-house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni-CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively. CONCLUSION: The low allergenicity of the newly developed low allergenic product "biscotti-twice baked-cake" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked-cake/muffin in patients who are reactive to once baked-milk products.

Shift from Cow's Milk Food Protein-Induced Enterocolitis Syndrome to IgE-Mediated Allergy: Case Series and Literature Review.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by gastrointestinal symptom onset within 1-4 hours from trigger food ingestion. In the literature, some authors have previously described the possibility that a patient with FPIES may develop an IgE-mediated allergy to the same trigger food, especially cow's milk (CM). Case Presentation: We reported five cases of CM-FPIES converting to IgE-mediated CM allergy presented at our tertiary pediatric Allergy Unit and performed a review of the literature, aiming to characterize the clinical features of patients who are at risk of developing such conversion. Conclusions: This phenomenon raises the question of whether IgE-mediated and non-IgE-mediated allergies represent a spectrum of the same disease and highlights the need for further investigation to understand the pathophysiological mechanisms of this process.

Exploring the Impact of Extra Virgin Olive Oil on Maternal Immune System and Breast Milk Composition in Rats.

Maternal breast milk plays a key role in providing newborns with passive immunity and stimulating the maturation of an infant's immune system, protecting them from many diseases. It is known that diet can influence the immune system of lactating mothers and the composition of their breast milk. The aim of this study was to establish if a supplementation during the gestation and lactation of Lewis rats with extra virgin olive oil (EVOO), due to the high proportion of antioxidant components in its composition, has an impact on the mother's immune system and on the breast milk's immune composition. For this, 10 mL/kg of either EVOO, refined oil (control oil) or water (REF group) were orally administered once a day to rats during gestation and lactation periods. Immunoglobulin (Ig) concentrations and gene expressions of immune molecules were quantified in several compartments of the mothers. The EVOO group showed higher IgA levels in both the breast milk and the mammary glands than the REF group. In addition, the gene expression of IgA in mammary glands was also boosted by EVOO consumption. Overall, EVOO supplementation during gestation and lactation is safe and does not negatively affect the mother's immune system while improving breast milk immune composition by increasing the presence of IgA, which could be critical for an offspring's immune health.

Impact of processing on the sensitising capacity and cross-reactivity of cow's and camel milk proteins in a Brown Norway rat study.

Infant formulas based on hydrolysed cow's milk proteins are used when breastfeeding is not feasible in cow's milk allergic infants. Camel milk has been shown to be well-tolerated by the majority of children with cow's milk allergy (CMA) and may be a substitute in management of CMA. Here we aimed to evaluate the impact of processing on immunogenicity, sensitising, antibody-binding and cross-reactive capacity of cow's and camel milk. Cow's and camel milk were processed by means of enzyme hydrolysis or heat treatment. Brown Norway rats were immunised with PBS, non-processed, enzyme hydrolysed or heat-treated cow's or camel milk. In vivo tests were performed for evaluation of clinical signs. Blood and faecal samples were analysed for levels and specificity of antibody responses. Cow's and camel milk showed similar sensitising capacity. Processing decreased the sensitising capacity of cow's milk, yet only enzyme hydrolysis but not heat treatment decreased the sensitising capacity of camel milk. Processing affected the specificity of antibodies raised in the rats, though the effect differed between cow's and camel milk. The study showed a low cross-reactivity between cow's and camel milk, which was decreased with processing, suggesting that processing of camel milk may improve its usefulness in CMA management.

Dietary Advancement Therapy Using Milk and Egg Ladders Among Children With a History of Anaphylaxis.

BACKGROUND: Anaphylaxis has been increasing in recent years, with common triggers in infants being milk and eggs. Currently, the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently, new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. OBJECTIVE: This study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. METHODS: Retrospective review of pediatric patients diagnosed with immunoglobulin E-mediated milk and/or egg allergy between 2011 and 2021. Inclusion and exclusion criteria were applied. Anaphylaxis was defined as per the World Allergy Organization-amended criteria 2020. Data analysis utilized SPSS Version 28. RESULTS: We reviewed 1,552 patient charts, and excluded 1,094, leaving a total sample size of 458. Seventy infants had anaphylaxis at diagnosis (milk n = 36; egg n = 34). A range of 77.8% to 85.2% of infants with anaphylaxis successfully completed the ladder, 88.9% to 92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. A range of 20.6% to 50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared with 17.3% to 40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. CONCLUSIONS: Milk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder; however, these children are less likely to complete the ladder, so parents should be educated in management of mild allergic reactions at home.

A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow's milk elimination diet.

INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.

Study protocol: The role of milk matrix lipids in programming the immunoreactivity of proteins derived from lactic acid bacteria.

Food allergy is widely recognized as a significant health issue, having escalated into a global epidemic, subsequently giving rise to the development of numerous additional complications. Currently, the sole efficient method to curb the progression of allergy is through the implementation of an elimination diet. The increasing number of newly identified allergens makes it harder to completely remove or avoid them effectively. The immunoreactivity of proteins of bacterial origin remains an unexplored topic. Despite the substantial consumption of microbial proteins in our diets, the immunologic mechanisms they might induce require thorough validation. This stands as the primary objective of this study. The primary objective of this study was to evaluate the effects of bacterial proteins on the intestinal barrier and immune system parameters during hypersensitivity induction in both developing and mature organisms. The secondary objective was to evaluate the role of lipids in the immunoreactivity programming of these bacterial proteins. Notably, in this complex, comprehensively designed in vitro, in vivo, and ex vivo trial, the immunoreactivity of various bacterial proteins will be examined. In summary, the proposed study intends to address the knowledge gaps regarding the effects of Lactobacillus microbial proteins on inflammation, apoptosis, autophagy, and intestinal barrier integrity in a single study.

Basophil allergen threshold sensitivity to casein (casein-specific CD-sens) predicts allergic reactions at a milk challenge in most but not all patients.

BACKGROUND: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges. METHODS: We enrolled 34 patients aged 5-15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined. RESULTS: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p < .001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p < .001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p = .041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = -0.418, p = .027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders. CONCLUSION: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.

Impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response post weaning time.

Milk is a whitish liquid that is secreted from mammary glands; and considered as the primary source of nutrition for newborns since they are not able to digest solid food. However, it contains primary nutrients, as well as growth and immune factors. Early weaning is a critical issue that face women and their babies in developing countries. To avoid infant malnutrition, they tend to use other milk types instead of baby formula. Therefore, the present study aimed to evaluate the impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response in male and female Sprague Dawley rats post weaning time. The amino acids, fatty acids, minerals and vitamins in the tested milk types were evaluated. Animals were divided into 5 groups (control, cow, buffalo, goat and camel milk administrated groups) (10 rats/group); each animal was administrated by 3.4 ml/day. Rats were administered with milk for 6 weeks; at the end of the 5th week, five animals of each group were isolated and the remaining five animals were immunized with sheep red blood cells (SRBCs) and kept for another week to mount immune response. The effect of different milk types on rats' immune response towards SRBCs was evaluated through pro-inflammatory cytokines, antioxidants, ESR and CRP measurement; together, with the histopathological examination of spleen samples and hemagglutination assay. Camel milk consumption reduced oxidative stress and inflammation in spleen that resulted from SRBCs immunization; in addition to, B cell stimulation that was apparent from the high level of anti-SRBCs antibodies. Camel milk is recommended for newborn consumption, due to its high-water content, unsaturated fatty acids, and vitamin C, as well as low lactose and fat content.

Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice.

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.

Lactic acid bacteria and yeast co-fermented milk alleviate cow milk allergy.

Cow milk allergy is one of the common food allergies. Our previous study showed that the allergenicity of fermented milk is lower than that of unfermented skimmed milk in vitro, and the antigenicity of ß-lactoglobulin and α-lactalbumin in fermented milk was decreased by 67.54% and 80.49%, respectively. To confirm its effects in vivo, allergic BALB/C mice model was used to further study the allergenicity of fermented milk. It was found that compared with the skim milk (SM) group, the intragastrically sensitization with fermented milk had no obvious allergic symptoms and the fingers were more stable: lower levels of IgE, IgG, and IgA in serum, lower levels of plasma histamine and mast cell protein-1, and immune balance of Th1/Th2 and Treg/Th17. At the same time, intragastrically sensitization with fermented milk increased the α diversity of intestinal microbiota and changed the microbiota abundance: the relative abundance of norank-f-Muribaculaceae and Staphylococcus significantly decreased, and the abundance of Lachnospiraceae NK4A136 group, Bacteroides, and Turicibacter increased. In addition, fermented milk can also increase the level of short-chain fatty acids in the intestines of mice. It turns out that fermented milk is much less allergenicity than SM. PRACTICAL APPLICATION: Fermentation provides a theoretical foundation for reducing the allergenicity of milk and dairy products, thereby facilitating the production of low-allergenic dairy products suitable for individuals with milk allergies.

Diagnostic accuracy of the Enferplex Bovine TB antibody test using individual milk samples from cattle.

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2-99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1-93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6-98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756-0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3-1077.5) and 0.092 (95% CI: 0.07-0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis.

Characterization of the potential allergenicity of enzymatically hydrolyzed casein in Balb/c mouse model.

Bovine casein is a major allergen present in cow milk to induce anaphylaxis. In this study, the potential allergenicity of enzymatically hydrolyzed casein (HC) was evaluated based on in vitro and in vivo. The results showed that Alcalase and Protamex treatment (AT, PT) reduced the potential allergenicity of CN, with the greatest reductions of 68.25% and 50.75%, respectively. In addition, in vivo results showed that HC effectively alleviated allergic response symptoms of Balb/c mice; a significant tendency toward decreased serum IgG1 and mast cell tryptase levels was observed, accompanied by a decrease of Th2-associated IL-4, IL-5, and IL-13 and an increase of IFN-γ levels in spleen. Moreover, the inflammation of the lung, jejunum, and ileum was remarkably ameliorated. The findings indicated that HC induced a shift toward Th1 response and maintained the Th1/Th2 immune balance. Importantly, our results provide the basis for the production of hypoallergenic dairy products.

Longitudinal Growth Trajectories in Children with Cow's Milk Allergy: Effects of Elimination Diet and Post-Termination Period.

INTRODUCTION: The primary dietary approach for managing cow's milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. METHODS: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow's milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. RESULTS: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). CONCLUSIONS: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers' growth.