Milk Allergy Research Articles

Long term outcome of IgE-mediated cow's milk allergy and risk factors for persistence

Resolution rates of IgE-mediated cow's milk allergy (IgE-CMA) by age 5 years, and risk factors for its persistence were previously described. To extend follow-up until the end of adolescence. An extension study of 23 of 54 patients diagnosed with IgE-CMA from a population-based study of 13,019 newborns, who remained allergic at age 5 years. Patients were examined at age 17 and their history reviewed. Resolution was determined by regular milk consumption without adverse reactions, or a negative oral food challenge (OFC). Allergy was defined by a recent objective reaction to milk and a positive skin prick test (SPT), or by sensitization ≥95% PPV to milk. Risk factors for persistence at age 17 were examined in the entire cohort. Of the 23 patients followed, 8/23 (35%) had spontaneous resolution, and 15 had persistent IgE-CMA. Overall, 39 (72.2%) of the 54 patients initially diagnosed with IgE-CMA had spontaneous resolution by age 17. Risk factors for IgE-CMA persistence at age 17 years included SPT >6 mm at time of diagnosis (p=0.03), no cow's milk formula feeding in the nursery (p=0.008), and wheezing on diagnostic OFC/initial reaction to milk (p=0.04). Seven patients experienced objective reactions after age 5 years. These patients had more wheezing (p=0.045) or anaphylaxis (p=0.02) on diagnostic OFC/initial reaction and more current asthma (p=0.007). Significant rate of spontaneous resolution of IgE-CMA still occurs beyond age 5 and few patients with IgE-CMA, mostly asthmatics, experience objective reactions by early adulthood. This should be considered in the treatment approach of IgE-CMA patients.

Clinical experience on the use of an extensively hydrolyzed formula (EHF) supplemented with purified lactose and human milk oligosaccharides (HMOS) for the management of cow’s milk protein allergy (CMPA) in primary care consultations of Spain. ELEVA study

Clinical experience on the use of an extensively hydrolyzed formula (EHF) supplemented with purified lactose and human milk oligosaccharides (HMOS) for the management of cow’s milk protein allergy (CMPA) in primary care consultations of Spain. ELEVA study

Cow's milk allergy treatment. An expert consensus

The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology.

Nutritional management of the pediatric patient with cow's milk protein allergy (CMPA) in primary care consultations from SPAIN. ELEVA study

Nutritional management of the pediatric patient with cow's milk protein allergy (CMPA) in primary care consultations from SPAIN. ELEVA study

Objectives for the use of raw materials and component composition for the production of low-lactose ice cream from goat milk

A huge number of people all over the world suffer from lactose intolerance. The second problem is an allergy to cow milk protein. People with lactose intolerance, as well as those who suffer from cow milk allergies, are forced to significantly limit their choice of ice cream or give it up completely. The article describes a solution to the problem of eating ice cream by children and adults suffering from lactose intolerance and an allergy to cow milk protein, and presents ways to overcome it.The goal of the research. Objectives for the use of raw materials and component composition for the production of low-lactose ice cream from goat milk. During the research, the quality indicators of the selected raw materials have been studied, the characteristics of the main ingredients for the production of low-lactose ice cream have been substantiated and given. Goat milk, in terms of its quality indicators, is most suitable for the production of ice cream, because it contains more protein, fat, solids, less lactose and does not cause allergies, and therefore it has been chosen as the main raw material for the production of ice cream. A theoretical and practical analysis of the chemical composition and properties of goat milk has been carried out, and compared with cow. To reduce the lactose content, a dual method of lactose hydrolysis has been chosen - the use of probiotic starter cultures and the lactase enzyme. In the process of combined hydrolysis at a temperature of 37-39⁰ C for 4-6 hours, a reduction in lactose content of less than 0.9% is achieved, while the concentration of cells of probiotic microorganisms in active form reaches 108 CFU/cm3. It is proposed to use the “Lactomix KM” stabilization system, which is usually used in the production of fermented milk products.

Prevention of allergies and infections by minimally processed milk in infants-The MARTHA feasibility and safety trial.

Consumption of raw cow's milk has repeatedly been shown to protect from asthma, allergies, and respiratory infections. As raw milk bears potential health hazards, it cannot be recommended for prevention. Therefore, we performed an intervention study with microbially safe but otherwise minimally processed cow's milk. Here we describe feasibility and safety of the trial. The MARTHA trial (DRKS00014781) was set up as a double-blind randomized intervention in a population residing in Bavaria. Infants from 6 to 36 months of age consumed minimally processed cow's milk (intervention arm) or ultra-heat-treated (UHT) semi-skimmed milk (comparator arm). At the age of 6 to 12 months, 260 infants were enrolled, with 72% having a family history of atopy. The extensive screening system for milk consumption and symptoms suggestive of adverse events was well accepted with 22,988 completed weekly surveys and an average completion of 82% surveys sent out. The children consumed the study milk on average on 457 days (61% of intervention days). The intervention proved to be safe without any case of milk allergy or milk intolerance under the intervention in both arms. All 6 cases of serious adverse events were unrelated to milk. The most common reason was unscheduled hospitalization of more than 3 days. The intervention with minimally processed milk and the study instruments proved feasible. During the age of 6 to 36 months, there was no increased risk of milk allergy in a population with a substantial proportion of family history of atopy.

Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a food allergy primarily affecting infants, often leading to vomiting and shock. Due to its poorly understood pathophysiology and lack of specific biomarkers, diagnosis is frequently delayed. Understanding FPIES genetics can shed light on disease susceptibility and pathophysiology-key to developing diagnostic, prognostic, preventive and therapeutic strategies. Using a well-characterised cohort of patients we explored the potential genome-wide susceptibility factors underlying FPIES. Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study. Notable genetic variants, including rs872786 (RBM8A), rs2241880 (ATG16L1) and rs2289477 (ATG16L1), were identified as significant findings in FPIES. A weighted SKAT model identified six other associated genes including DGKZ and SIRPA. DGKZ induces TGF-β signalling, crucial for epithelial barrier integrity and IgA production; RBM8A is associated with thrombocytopenia absent radius syndrome, frequently associated with cow's milk allergy; SIRPA is associated with increased neutrophils/monocytes in inflamed tissues as often observed in FPIES; ATG16L1 is associated with inflammatory bowel disease. Coexpression correlation analysis revealed a functional correlation between RBM8A and filaggrin gene (FLG) in stomach and intestine tissue, with filaggrin being a known key pathogenic and risk factor for IgE-mediated food allergy. A transcriptome-wide association study suggested genetic variability in patients impacted gene expression of RBM8A (stomach and pancreas) and ATG16L1 (transverse colon). This study represents the first case-control exome association study of FPIES patients and marks a crucial step towards unravelling genetic susceptibility factors underpinning the syndrome. Our findings highlight potential factors and pathways contributing to FPIES, including epithelial barrier dysfunction and immune dysregulation. While these results are novel, they are preliminary and need further validation in a second cohort of patients.

Time Trends, Regional Variation and Associations of Low-Allergy Formula Prescribing in England.

Cow's milk allergy (CMA) overdiagnosis appears to be increasing and is associated with excessive low-allergy formula prescription. We evaluated recent trends and regional variation in low-allergy formula prescribing for CMA in England, and assessed potential risk factors for higher prescribing rates. Data on national and regional prescribing of low-allergy formulas were extracted from England's electronic prescription database using R. Region-level factors were evaluated for potential associations with regional low-allergy formula prescription rates using multivariate linear regression. Analysis of national prescribing trends covered 2007-2023, analysis of regional variation and region-level factors examined 2017-2019, prior to a re-organisation of the regional healthcare structure in England. Low-allergy formula prescribing increased from 6.1 to 23.3 L per birth nationally, between 2007 and 2023. Regional prescribing rate varied from 0.8 to 47.6 L per birth in 2017-2019. We found significant associations between regional low-allergy formula prescribing rate and regional prescribing rates for milk feed thickeners Gaviscon Infant and Carobel Instant (β = 0.10, p < 0.01), and for other anti-reflux medications used in young children (β = 0.89 p < 0.01). Inconsistent associations were seen with prescribing junior adrenaline auto-injectors and oral antibiotics. A model including these four variables accounted for 37% of regional variation in low-allergy formula prescribing rate. Region-level socio-economic deprivation, CMA guideline recommendations and paediatric allergy service provision were not associated with low-allergy formula prescribing. Low-allergy formula prescribing in England is increasing, varies significantly by region and is consistently associated with prescribing rates for milk feed thickeners and other anti-reflux medication for young children. Community prescribing behaviours may be important determinants of CMA overdiagnosis.

Assessment of the effect of lactic acid bacteria fermentation on IgE-/IgG-binding ability and nutritional properties of cow milk.

Cow milk (CM) is an important food source for humans, and food allergy caused by CM has attracted attention worldwide. To our knowledge, systematic studies about the effects of Lactobacillus paracasei, Lactobacillus plantarum, and Pediococcus pentosaceus on the IgE-/IgG-binding ability and nutritional properties of CM are very rare. In this study, L. paracasei, L. plantarum, and P. pentosaceus fermentation on the IgE-/IgG-binding ability was determined by Enzyme-Linked Immunosorbent Assay (ELISA), and the protein quality, amino acid profile, and color were systematically evaluated. The results showed that these LAB strains exhibited higher protein degradation ability, and the IgE reactivity reduction rate was 41.03%-60.00% and the IgG reduction rate was 29.86%-67.20%, respectively. Additionally, the nutritional value was improved obviously, and the color was altered significantly, which was conductive to develop dairy products. These findings provided a theoretical foundation for the development of hypoallergenic dairy products. PRACTICAL APPLICATION: In this study, L. paracasei, L. plantarum and P. pentosaceus could be considered as good potential candidates for solving cow milk allergy owing to their decreased IgE/IgG binding ability andimproved nutritional and sensory properties, which provide a promising strategy to develop hypoallergenic dairy products.

Is there sufficient evidence to support the health benefits of including donkey milk in the diet?

Donkey milk has attracted attention due to its distinctive nutritional composition and potential health advantages, particularly because of its whey protein content, which includes lysozyme, α-lactalbumin, lactoferrin, and β-lactoglobulin and vitamin C, among other components. These elements contribute to immunoregulatory, antimicrobial, antioxidant, and anti-inflammatory properties, positioning donkey milk as a possible therapeutic option. In addition, due to the low levels of caseins, the casein-to-whey protein ratio, and the β-lactoglobulin content in donkey milk, it presents an optimal alternative for infant formula for individuals with cow's milk allergies. Moreover, research into donkey milk's potential for cancer prevention, diabetes management, and as a treatment for various diseases is ongoing, thanks to its bioactive peptides and components. Nevertheless, challenges such as its low production yield and the not fully understood mechanisms behind its potential therapeutic role necessitate more thorough investigation. This review consolidates the existing knowledge on the therapeutic possibilities of donkey milk, emphasizing its importance for human health and the need for more detailed studies to confirm its health benefits.

Gut microbiome features in pediatric food allergy: a scoping review.

Increasing evidence suggests that alterations in the gut microbiome (GM) play a pivotal role in the pathogenesis of pediatric food allergy (FA). This scoping review analyzes the current evidence on GM features associated with pediatric FAs and highlights the importance of the GM as a potential target of intervention for preventing and treating this common condition in the pediatric age. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched PubMed and Embase using the keywords (gut microbiome OR dysbiosis OR gut microbiota OR microbiome signatures) AND (food allergy OR IgE-mediated food allergy OR food protein-induced allergic proctocolitis OR food protein-induced enterocolitis OR non-IgE food allergy OR cow milk allergy OR hen egg allergy OR peanut allergy OR fish allergy OR shellfish allergy OR tree nut allergy OR soy allergy OR wheat allergy OR rice allergy OR food sensitization). We included 34 studies reporting alterations in the GM in children affected by FA compared with healthy controls. The GM in pediatric FAs is characterized by a higher abundance of harmful microorganisms (e.g., Enterobacteriaceae, Clostridium sensu stricto, Ruminococcus gnavus, and Blautia spp.) and lower abundance of beneficial bacteria (e.g., Bifidobacteriaceae, Lactobacillaceae, some Bacteroides species). Moreover, we provide an overview of the mechanisms of action elicited by these bacterial species in regulating immune tolerance and of the main environmental factors that can modulate the composition and function of the GM in early life. Altogether, these data improve our knowledge of the pathogenesis of FA and can open the way to innovative diagnostic, preventive, and therapeutic strategies for managing these conditions.

Evolutive Study of Dietary Aspects and Intestinal Microbiota of Pediatric Cohort with Cow's Milk Protein Allergy.

One of the most common food allergies in the pediatric population is allergy to cow's milk protein (CMPA). Treatment consists of avoiding cow's milk proteins in lactating mothers and/or using therapeutic formulas based on hydrolysates or vegetable formulas. In infants with CMPA at diagnosis, a different gut microbial profile has been found compared to healthy children, with a reduction in beneficial bacteria. The aim of this study was to evaluate changes in the gut microbiota profile and its metabolites, dietary patterns and anthropometric variables in a pediatric cohort with CMPA after six months on a restrictive diet compared to healthy controls. In total, 21 patients diagnosed with CMPA and a control group of 24 healthy infants participated in this study. The fecal microbiota of all participants were investigated by metataxonomic analysis of 16S rDNA amplicons, and fecal short-chain fatty acids were measured by gas chromatography. Epidemiological assessment and dietary questionnaires were carried out for both groups. Regarding growth, no significant differences were found, but differences in dietary intake of some macro- and micronutrients were observed. Patients who were breastfed at six months had higher bifidobacteria and lipid intakes than patients fed with hydrolyzed formulas. Although the growth of CMPA infants fed with therapeutic formula is similar to breastfed CMPA infants, there are differences in microbiota composition and macronutrient intake that underline the importance of continued breastfeeding in CMPA cases.

Milk allergy tapered to dahi culture

Milk allergy tapered to dahi culture

β-Lactoglobulin Separation from Whey Protein: A Comprehensive Review of Isolation and Purification Techniques and Future Perspectives

Cow milk, although rich in essential nutrients, is a well-known allergic food that can cause allergic reactions in infants and young children. β-Lactoglobulin accounts for 10% of the total protein in milk and 50% of the whey protein, which has high nutritional value and excellent functional properties but is also the main allergen leading to milk protein allergy. Exploring the mechanism of milk allergy and selecting suitable separation and purification methods to obtain high-purity β-Lactoglobulin is the premise of research on reducing allergenicity. In this review, the research progress in membrane technology, gel filtration chromatography, ion exchange chromatography, affinity chromatography, precipitation and aqueous 2-phase system separation for the separation and purification of milk β-Lactoglobulin is reviewed in detail to promote the further development of milk β-Lactoglobulin separation and purification methods and provide a new method for the development of hypoallergenic dairy products in the future. Among these methods, ion exchange chromatography and gel chromatography are widely used, precipitation is generally used as a crude purification step, and high-performance liquid chromatography and membrane technology are used for further purification to improve the purity of allergens.

Validity of Cow's Milk-related Symptom Score among Children suspected to have Cow's Milk protein Allergy

Validity of Cow's Milk-related Symptom Score among Children suspected to have Cow's Milk protein Allergy

Evaluate the Frequency of EosinophilicEsophagitisin Individuals with Refractory GERD

Background: Theeosinophilic infiltrate of the esophagus mucosal distinguishes the esophageal ailment known as Eosinophilicesophagitis (EoE). This study aims to determine the frequency of EoE in patients with gastroesophageal reflux disease (GERD), a gastro esophageal reflux condition that is persistent. Methods: The 248 children in total hadelectiveupper gastrointestinal endoscopy (UGIE) during the study period were separated in tosix groups: individuals without a history of steroid usage and those with outanesophageal biopsyforthrombocytopenia. As a result, 200 people participated in the study total. Results: After an evaluation of 200 children having elective UGIE, A variety of health problems were found during the investigation, including food bolusimpact (2 %), achalasia cardia (5 %), pepticstricture (6 %), congenitalstricture (3 %), post-esophageal atresia repairanastomoticstricture (4 %), and symptoms of gastro esophageal reflux, including vomiting (10 %), regurgitation (2 %), belchingchest (1,5 %), nocturnal cough (2,5 %), pain/heartburn (12,5 %), and feeding refusal (1 %). There were several unusual illnesses that were observed, including Crohn's disease accounted for 2 %, paediatric intestinal pseudo-obstruction (10 %), abdominal discomfort (17,5 %), celiacdisease (16 %), cow's milk protein allergy (3 %), and un classified IBD (7 %). Conclusion: EoEfrequently affects GERD patients who are recalcitrant to treatment. Dysphagia, food impaction, and heartburn are posible symptoms. EGD and esophageal biopsy should be explored for EoEscreening in elderly individuals with strong GERD who are atopy positive and who have not responded to gastric acid inhibitors.

Specific Gut Microbiome Signatures in Children with Cow's Milk Allergy.

Although gut dysbiosis is associated with cow's milk allergy (CMA), causality remains uncertain. This study aimed to identify specific bacterial signatures that influence the development and outcome of the disease. We also investigated the effect of hypoallergenic formula (HF) consumption on the gut microbiome of milk-allergic children. 16S rRNA amplicon sequencing was applied to characterize the gut microbiome of 32 milk-allergic children aged 5-12 years and 36 age-matched healthy controls. We showed that the gut microbiome of children with CMA differed significantly from that of healthy children, regardless of whether they consumed cow's milk. Compared to that of healthy cow's milk consumers, it was depleted in Bifidobacterium, Coprococcus catus, Monoglobus, and Lachnospiraceae GCA-900066575, while being enriched in Oscillibacter valericigenes, Negativibacillus massiliensis, and three genera of the Ruminococcaceae family. Of these, only the Ruminococcaceae taxa were also enriched in healthy children not consuming cow's milk. Furthermore, the gut microbiome of children who developed tolerance and had received an HF was similar to that of healthy children, whereas that of children who had not received an HF was significantly different. Our results demonstrate that specific gut microbiome signatures are associated with CMA, which differ from those of dietary milk elimination. Moreover, HF consumption affects the gut microbiome of children who develop tolerance.

A comparison of the physicochemical properties, allergenicity, and stability of recombinant β-lactoglobulin: Development of standard bovine milk allergens

Bovine milk is one of the eight major allergenic foods identified by WHO/FAO, and β-lactoglobulin (BLG) is the primary allergen. Allergen standardization is very important for the diagnosis of milk allergy, and recombinant protein preparation is a promising method. In this study, BLG with high soluble expression was prepared by a method based on Escherichia coli. To verify the feasibility of recombinant BLG, the difference in physicochemical properties, allergenicity, and stability were investigated. Recombinant and natural BLG both had a size of approximately 230 nm with a zeta potential of −50 mV, indicating that they share the similar solubility and colloidal properties. Additionally, allergic mice model results confirmed that recombinant BLG showed comparable ability in stimulating antibody production, Th2 cytokine release, and cellular immunity compared with natural BLG. Then, the thermal stability of BLG was studied using spectrum analysis within the range of 25–85 °C. Recombinant BLG showed satisfactory thermal stability, the concentration, protein structure and IgG binding capacity changed obviously until temperature reached at 55 °C, although natural BLG is more heat resistant. After 28 days storage at 4 °C in the form of lyophilized powder, there was no significant change in the content of recombinant and natural BLG. In summary, the physicochemical properties, allergenicity, and stability of recombinant BLG were comparable to those of natural BLG. This study provides theoretical reference for the development of standard bovine allergen, and it is expected that recombinant allergen can be used in the research and diagnosis of bovine milk allergy.

The Cow's Milk-Related Symptom Score (CoMiSSTM) in Presumed Healthy Egyptian Infants.

The Cow's Milk-Related Symptom Score (CoMiSS) was created as an awareness tool for cow's milk-related symptoms. After different trials, a score of ≥10 was selected to raise awareness. The CoMiSS in healthy infants needs to be determined because the score does not return to 0 during a diagnostic elimination diet. This study aims to establish normal values in healthy Egyptian infants. In this prospective cross-sectional study, pediatricians determined the CoMiSS in healthy infants ≤ 12 months. Infants seeking medical help due to cow's milk allergy (CMA) symptoms and infants with any known or suspected diseases, preterm delivery, medication, or food supplements were excluded. A total of 808 infants were included with a median (Q1; Q3) age of 7 (3;10) months (50.7% boys). The median (Q1; Q3) CoMiSS was 5 (5;6). The 95th percentile was 7. There was no significant difference in the median CoMiSS according to gender (p = 0.621) or due to breastfeeding exclusively (p = 0.603). A significant difference was seen in the CoMiSS according to age, although all the age categories had a median CoMiSS of 5. This study revealed the median CoMiSS is 5 in presumed healthy Egyptian infants aged 0-12 months. The CoMiSS was not dependent on feeding. The determination of the CoMiSS in healthy infants allows for the determination of a cut-off under which CMA is unlikely, and a cut-off to raise awareness of CMA, thereby preventing under- and overdiagnosis. Since the median CoMiSS was not different in European infants, the outcome suggests that the CoMiSS may be a reliable awareness tool for CMA independent of ethnicity. However, additional studies are needed to confirm the previous hypothesis.

Difficulties in diagnosing non-IgE-dependent gastrointestinal forms of food allergy: How informative is fecal calprotectin?

The prevalence of allergic diseases is increasing at rates corresponding to epidemic’s spread rates. Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Its clinical variants remain hard-to-diagnose diseases due to their multiple clinical faces. Food allergy can develop along the pathway associated with both IgE and non-IgE, or mixed one. Non-IgEassociated variants of food allergies, due to the lack of accurate and specific laboratory markers, can cause significant difficulties in making a diagnosis. The search for new diagnostic markers continues. Faecal calprotectin, a calcium-binding leukocyte protein consisting of a complex of two monomers S100A8 and S100A9, may be one of them. Faecal calprotectin concentration is directly proportional to the number of leukocytes migrating into the intestinal wall, due to which faecal calprotectin becomes an accurate, non-invasive and sensitive indicator reflecting the level of inflammation in the intestines. Today, serum and faecal calprotectin are used as laboratory markers, and the latter, being more accessible and not critical for collection material is widely known as a diagnostic marker of inflammatory bowel diseases. Some studies suggest that faecal calprotectin may be used to diagnose cow’s milk protein allergy in young infants when other diagnostic tests are not available. Data from various studies remain contradictory. Further studies to investigate the possibilities of using faecal calprotectin as a marker of the gastrointestinal food allergy in young children is needed.