Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.

Association Between Breastmilk Microbiota and Food Allergy in Infants

Regulating the composition of human breastmilk has the potential to prevent allergic diseases early in life. The composition of breastmilk is complex, comprising varying levels of oligosaccharides, immunoactive molecules, vitamins, metabolites, and microbes. Although several studies have examined the relationship between different components of breastmilk and infant food allergies, few have investigated the relationship between microorganisms in breastmilk and infant food allergy. In the present study, we selected 135 healthy pregnant women and their full-term newborns from a cohort of 202 mother–infant pairs. Among them, 69 infants were exclusively breastfed until 6 mo after birth. At follow-up, 11 of the 69 infants developed a food allergy in infancy while 22 showed no signs of allergy. Thirty-three breastmilk samples were collected within 1 mo after delivery, and 123 infant fecal samples were collected at five time points following their birth. These samples were analyzed using microbial 16S rRNA gene sequencing. The abundance and evenness of the milk microbiota and the number of differential bacteria were higher in the breastmilk samples from the non-allergy group than in those from the food allergy group. The non-allergy group showed relatively high abundance of Bifidobacterium, Akkermansia, Clostridium IV, Clostridium XIVa, Veillonella, and butyrate-producing bacteria such as Fusobacterium, Lachnospiraceae incertae sedis, Roseburia, and Ruminococcus. In contrast, the abundance of Proteobacteria, Acinetobacter, and Pseudomonas in breastmilk was higher in the food allergy group. A comparison of the changes in dominant differential breastmilk microbiota in the intestinal flora of the two groups of infants over time revealed that the changes in Bifidobacterium abundance were consistent with those in the breastmilk flora. Functional pathway prediction of breastmilk microflora showed that the enhancement of the metabolic pathways of tyrosine, tryptophan, and fatty acids was significantly different between the groups. We suggest that changes in the breastmilk microbiota can influence the development of food allergies. Breastmilk contains several microbes that have protective effects against food allergies, both by influencing the colonization of intestinal microbiota and by producing butyrate. This study may provide new ideas for improving infant health through early intervention with probiotics.

Protein linking fatty acids and its genetic regulation in children having food allergy

Objective: Study the effect of the Ala54Thr FABP gene polymorphism on the produce of the intestinal FABP fraction in blood serum. urine and coprofiltrate in children having food allergies.Methods: The content of the FABP intestinal fraction in urine, feces, and blood serum was determined using ELISA method. The study of FABP genes polymorphism (G163A, Ala54Thr) was carried out using PCR method.Results: Statistically significant increase of the FABP level in blood serum, urine and feces in children with FA was detected in various biological fluids. The distribution of FABP2 alleles and genotypes obeyed the Hardy-Weinberg law (χ 2 = 0; p = 1,000) and did not significantly differ from the distribution of genotypes in children having FA andin the control sample (p = 0.638).Conclusions: The study did not reveal an association of the pathological genotype FABP G163A, (Ala54Thr) with the hyperproduction of the FABP intestinal fraction in children having FA, confirming the diagnostic significance of this marker increase during exacerbation of the disease.

Food allergens: threshold levels and methodologies for risk management

Food allergies and allergen management are important problems of the public health and food industry. The idea of determining allergen concentrations in food ingredients and food products that are capable of causing severe allergic reactions is of great interest for regulatory bodies as well as consumer associations and the industry all over the world. In this connection, scientists proposed different approaches to determining the basis for assessment of severity of risks of food allergens for health of patients suffering from food allergy similar to methods of risk assessment for other hazards associated with food products (for example, chemical, microbiological). To assess risk of allergens, three different approaches were proposed: i) traditional risk assessment using the no observed adverse effect level (NOAEL)) and uncertainty factors; (ii) approach based on the benchmark dose (BMD)) and margin of exposure (MoE)); and (iii) probability models. These approaches can be used in risk management in food production and in the development of warning marking about the presence of allergens. The reliability of risk assessment will depend on a type, quality and quantity of data used for determining both population threshold levels (or threshold distributions) and an impact of an allergenic product/ingredient on a particular individual.

Glycation end products and technological aspects of reducing immunogenicity of specialized food products for nutrition of athletes

Food allergy, which affects about 8% of children and 5% of adults in the world, is one of the major global health problems, and allergen control is an important aspect of food safety. According to the FALCPA (Food Allergen Labeling and Consumer Protection Act of 2004 FDA), more than 160 foods can cause allergic reactions, with eight of them responsible for 90% of all food allergies in the United States, including milk, eggs, wheat, peanuts, soybeans, tree nuts, crustaceans and fish, also known as the Big 8. Most foods that are sources of obligate allergens are heat treated before consumption, which can trigger the Maillard reaction, which produces glycation end products. Symptoms of food sensitization are known to significantly affect the quality of life, gut microbial diversity and adaptation potential. In particular, in athletes, this can be expressed in a decrease in the effectiveness of the training process, which leads to poor endurance and athletic performance. In this regard, it seems relevant to study the effect of the Maillard reaction and AGEs on the immunogenicity of proteins and the possible relationship between these compounds and food allergy, as well as to develop measures to prevent the adverse effect of allergens on the body of a professional athlete and any other consumer.

Epicutaneous sensitization. what do we know?

Background. According to the currently existing hypothesis, epicutaneous sensitization is one of the leading mechanisms in the development of food allergy.The aim of this review was to analyze immune mechanisms in epicutaneous sensitization and the role of skin barrier impairment.We performed a literature search using PubMed, UpToDate, Web of Science, and Scopus databases by the key words: epicutaneous sensitization, atopic dermatitis, skin barrier impairment, food allergy. Articles were to be in open access and present the most relevant information on the topic. Studies were selected by the largest sample size and the highest citation index. Once publications were identified, they were reviewed by all the authors to select the studies that specifically addressed the theme of the review. A total of 101 publications from 1998–2000 were included in the study.This review article discusses the data of experimental studies, sets out modern ideas about the hypothesis of a double exposure to an allergen, and presents research data proving the clinical significance of epicutaneous sensitization in relation to food allergy. Knowledge about the mechanisms of epicutaneous sensitization development is necessary to elaborate strategies for prevention of food allergy. One of the modern trends in prevention is the use of emollients, which are supposed to restore the skin response. However, studies on preventive intake of emollients do not present a similar viewpoint.There is not enough evidence for or against the mechanism of epicutaneous sensitization as an indispensable condition for the formation of food allergies. Further research in this area is required.

Food allergy knowledge, attitudes, and practices of food handlers working in the five-star hotel kitchens in Turkey

The purpose of this study is to determine the food allergy knowledge, attitudes and practices of food handlers working in five-star hotel kitchens in Turkey and to explore the association between the obtained scores and handlers’ demographic and working characteristics. A cross-sectional survey involving 450 food handlers in the state of Istanbul, Ankara and Antalya, in Turkey, was conducted using a paper-based questionnaire. The total knowledge score of the participants was 11.89 ±2.22 (max 17), attitude score 60.63 ±10.34 (max 75) and practice score 55.60 ±8.01 (max 65). In the comparison based on demographic characteristics; the knowledge (12.10 ±2.15) and practice (56.33 ±5.91) scores of the food handlers who received food allergy training in the hotel they work were found to be significantly higher than those who did not receive food allergy training (p<0.05). Food allergy knowledge of food handlers was evaluated as "average", attitude as "positive", and practice as "low risk practice". The results obtained are expected to contribute to the development of food allergy policies, procedures, and the planning of the necessary trainings for reducing the risks of food allergies and preventing fatal allergic reactions.