[A CHILD CASE OF EGOMA (PERILLA FRUTESCENS) ALLERGY DUE TO SCHOOL LUNCH, PROBABLY CAUSED BY PERCUTANEOUS SENSITIZATION].

Herein, we report the case of a 7-year-old girl with a history of atopic dermatitis because of infancy. Her grandfather grew Egoma (Perilla frutescens), and her family frequently consumed food items prepared using Egoma; however, she never consumed them because she did not enjoy these food items; she experienced vomiting, facial swelling, and oral discomfort upon ingesting Egoma during school lunch for the first time. Her food oral challenge test was positive, as well as a skin-prick test with sesame powder. Egoma antigen protein was extracted and reacted with patient serum by immunoblotting, which detected a positive band of approximately 26kDa. She was brought up in an environment with high exposure to Egoma; hence, she most likely developed an allergy to Egoma because of percutaneous sensitization. This is the first time an Egoma allergen analysis has been conducted in Japan, and we consider it to be a valuable case.

Novel Perspective on the Regulation of Offspring Food Allergy by Maternal Diet and Nutrients.

There has been a dramatic surge in the prevalence of food allergy (FA) that cannot be explained solely by genetics, identifying mechanisms of sensitization that are driven by environmental factors has become increasingly important. Diet, gut microbiota, and their metabolites have been shown to play an important role in the development of FA. In this review, we discuss the latest epidemiological evidence on the impact of two major dietary patterns and key nutrients in early life on the risk of offspring developing FA. The Western diet typically includes high sugar and high fat, which may affect the immune system of offspring and increase susceptibility to FA. In contrast, the Mediterranean diet is rich in fiber, which may reduce the risk of FA in offspring. Furthermore, we explore the potential mechanisms by which maternal dietary nutrients during a window of opportunity (pregnancy, birth, and lactation) influences the susceptibility of offspring to FA through multi-interface crosstalk. Finally, we discuss the limitations and gaps in the available evidence regarding the relationship between maternal dietary nutrients and the risk of FA in offspring. This review provides novel perspective on the regulation of offspring FA by maternal diet and nutrients.

An overview of a preliminary multicenter retrospective study on food and drug allergies in Moroccan pediatric population.

Introduction: this study aimed to investigate the prevalence and management of food allergies (FA) and drug allergies (DA) in Morocco. Sparse and conflicting epidemiological data exist on the exact prevalence of allergies in the country. The rise in allergies can be attributed to various factors. Methods: the study analyzed data from patients with suspected FA and DA who sought medical attention. Statistical tests were used to analyze the data, percentages were computed for qualitative variables, and for quantitative variables, medians or means accompanied by standard deviations (SD) were calculated. The Chi-square test was employed to assess categorical variables. A p-value < 0.05 was considered statistically significant. Results: Cow's milk was the most reported food allergen (58.2%), followed by egg and nuts (23.4% and 12.1%, respectively). The most affected age group was children under 5 years. Antibiotics were the leading cause of reported drug allergies (44.8%), particularly Beta-lactams. Immediate reactions were commonly associated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms of FA included acute urticaria, vomiting, anaphylactic shock, and facial edema. Urticaria was the most frequent symptom of DA. Antihistamines and corticosteroids were the main treatments used for both FA and DA. Conclusion: the prevalence of FA and DA in Morocco remains uncertain due to limited data. There is a need for centralized data collection and awareness among clinicians and the general population regarding allergies. The study highlights the importance of proper diagnosis and management of allergies to ensure patient safety. The findings emphasize the necessity of establishing a mandatory center for allergy care in Morocco to improve the understanding and management of allergic conditions.

[Anaphylaxis due to legumes: case report]. / Anafilaxia por leguminosas: reporte de un caso.

BACKGROUND: Legumes belonging to the family Fabaceae of the order Fabales are a widely consumed source of protein. IgE-mediated hypersensitivity reactions to legumes have been described, the most studied allergens being peanuts and soybeans. In the Mediterranean region and India, lentils, chickpeas and peas have been considered important allergens and legumes have been reported to represent the fifth most common cause of food allergy in children under 5 years of age in Spain. In Latin America, there are few reports of allergy to legumes other than peanuts, and these are especially in the paediatric population. OBJECTIVE: To describe a case of IgE-mediated legume allergy in an adult female patient. CASE REPORT: We describe the case of a 65-year-old female patient who reports a 20-year history of generalized urticaria, accompanied by angioedema and dyspnea occurring immediately after consumption of lentils, beans, chickpeas, soya beans and cold meats, requiring admission to the emergency department for this cause. Tolerates peanuts. She does not report anaphylaxis in any context other than those described. He has presented generalized pruritus with exposure to fumes from cooking beans. Pathological history: Hypertension, type II diabetes mellitus, hypothyroidism. Allergic: Anaphylaxis due to penicillin at the age of 30. Other history: extensive local reaction to hymenoptera sting. Prick test trophoallergens: soya 3 mm. Prick to prick protein based on commercial soybean 7mm, chickpea 5mm, lentil 6mm and bean 7mm. He was negative for wheat and peanut (Image 1) (Attached in separate file). It has a normal tryptase report. Indication was given for adequate adrenaline and strict avoidance of legumes, except peanuts. CONCLUSIONS: Legume allergy is little known in our environment and mainly affects children. Clinical manifestations include mild reactions and anaphylaxis. A high degree of cross-reactivity among legumes has been reported. Lentils have cross-reactivity with chickpeas and beans. Peanut allergy may also be associated with allergy to lentils, chickpeas, and peas, but is less frequently reported.

ANTECEDENTES: Las leguminosas pertenecientes a la familia Fabaceae del orden Fabales, son una fuente de proteína de amplio consumo. Se han descrito reacciones de hipersensibilidad mediadas por IgE a las leguminosas, siendo los alérgenos más estudiados el maní y la soya. En la región mediterránea y en India, las lentejas, garbanzos y arvejas se han considerado alérgenos importantes, y se ha informado que las leguminosas representan la quinta causa más común de alergia alimentaria en niños menores de cinco años en España. En América Latina, hay pocos reportes de alergia a las leguminosas diferentes al maní, y éstos son, especialmente, en población pediátrica. OBJETIVO: Describir el caso de alergia mediada por IgE a leguminosas, en una paciente adulta. REPORTE DE CASO: Se describe el caso de una paciente de 65 años, quien reporta un cuadro de 20 años con evolución consistente de urticaria generalizada, acompañada de angioedema y disnea, que ocurre, en forma inmediata, tras el consumo lentejas, fríjoles, garbanzos, soya y carnes frías; y requiere de ingresos al servicio de urgencias por esta causa. Tolera maní. No se reporta anafilaxia en otro contexto diferente a los descritos. Ha presentado prurito generalizado con la exposición a vapores de la cocción de fríjoles. Antecedentes patológicos: hipertensión arterial, diabetes mellitus tipo II, hipotiroidismo. Alérgicos: Anafilaxia por Penicilina a los 30 años. Otros antecedentes: Reacción local extensa con picadura de himenópteros. Prick test trofoalérgenos: soya 3 mm. Prick to prick proteína a base de soya comercial 7mm, garbanzo 5mm, lenteja 6mm y fríjol 7mm. Fue negativa para trigo y maní (Imagen 1). (Adjunta en archivo separado). Tiene reporte de triptasa normal. Se dio indicación de porte adecuado de adrenalina y evitación estricta de leguminosas, excepto maní. CONCLUSIONES: La alergia a las leguminosas es poco conocida en nuestro medio, y afecta principalmente a los niños. Sus manifestaciones clínicas incluyen reacciones leves y anafilaxia. Se ha informado, un alto grado de reactividad cruzada entre las leguminosas. Las lentejas tienen reactividad cruzada con garbanzos y fríjoles. La alergia al maní también puede estar asociada con la alergia a lentejas, garbanzos y guisantes, pero se informa con menos frecuencia.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

Dietary Intervention during Weaning and Development of Food Allergy: What Is the State of the Art?

Food allergy (FA) affects approximately 6-8% of children worldwide causing a significant impact on the quality of life of children and their families. In past years, the possible role of weaning in the development of FA has been studied. According to recent studies, this is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collect the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food. As shown in most of the studies included in this review, early food introduction did not show a potential protective role against FA development, and we conclude that further evidence is needed from future clinical trials.

A Review of Shared Decision-Making, Published Protocols, and Post-desensitization Strategies in Oral Immunotherapy (OIT).

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Allergic Reaction to a Commercially Available Insect Snack Caused by House Cricket (Acheta domesticus) Tropomyosin.

SCOPE: Edible insects contain allergens with potential cross-reactivity to other invertebrates. Here, this study examines IgE-reactive proteins in a house cricket snack (Acheta domesticus) leading to an allergic reaction in a 27-year old man followed by a similar reaction days later after eating shrimps. METHODS AND RESULTS: Prick to prick tests verify the IgE-mediated allergy to crickets and skin prick testing confirms a type I sensitization to house dust mite without any clinical relevance for the patient, and to shrimp extracts, but is negative for several other foods. Serological testing reveals a sensitization to shrimps, shrimp tropomyosin, and house dust mite tropomyosin. IgE-immunodetection shows that the cricket allergic patient is sensitized to two proteins of 45 and >97 kDa using aqueous control cricket extract, but to only one protein at around 45 kDa when using the causative, seasoned insect snack extract. Mass spectrometry data and IgE-inhibition experiments clearly identify this protein belonging to the tropomyosin allergen family. CONCLUSION: This case report suggests that cricket tropomyosin may be an elicitor of allergic reactions even in previously not allergic patients, although it cannot be excluded the patient reacted additionally to other ingredients of the snack.

Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Food allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy. METHODS AND ANALYSIS: This paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval. PROSPERO REGISTRATION NUMBER: CRD42022373015.

The Future of Food Allergy Management: Advancements in Therapies.

PURPOSE OF REVIEW: To review current and future treatment options for IgE-mediated food allergy. RECENT FINDINGS: Recent years have seen major developments in both allergen-specific and allergen-non-specific treatment options, with the first FDA-approved peanut oral immunotherapy (OIT) product becoming available in 2020. In addition to OIT, other immunotherapy modalities, biologics, adjunct therapies, and novel therapeutics are under investigation. Food allergy is a potentially life-threatening condition associated with a significant psychosocial impact. Numerous products and protocols are under investigation, with most studies focusing on OIT. A high rate of adverse events, need for frequent office visits, and cost remain challenges with OIT. Further work is needed to unify outcome measures, develop treatment protocols that minimize adverse events, establish demographic and clinical factors that influence candidate selection, and identify patient priorities.

The Natural History and Risk Factors for the Development of Food Allergies in Children and Adults.

PURPOSE OF REVIEW: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. RECENT FINDINGS: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.

A comprehensive review on mango allergy: Clinical relevance, causative allergens, cross-reactivity, influence of processing techniques, and management strategies.

Mangoes (Mangifera indica) are widely prized for their abundant nutritional content and variety of beneficial bioactive compounds and are popularly utilized in various foods, pharmaceuticals, and cosmetics industries. However, it is important to note that certain proteins present in mango can trigger various allergic reactions, ranging from mild oral allergy syndrome to severe life-threatening anaphylaxis. The immunoglobulin E-mediated hypersensitivity of mango is mainly associated with three major allergenic proteins: Man i 1 (class IV chitinase), Man i 2 (pathogenesis-related-10 protein; Bet v 1-related protein), and Man i 4 (profilin). Food processing techniques can significantly affect the structure of mango allergens, reducing their potential to cause allergies. However, it is worth mentioning that complete elimination of mango allergen immunoreactivity has not been achieved. The protection of individuals sensitized to mango should be carefully managed through an avoidance diet, immediate medical care, and long-term oral immunotherapy. This review covers various aspects related to mango allergy, including prevalence, pathogenesis, symptoms, and diagnosis. Furthermore, the characterization of mango allergens and their potential cross-reactivity with other fruits, vegetables, plant pollen, and seeds were discussed. The review also highlights the effects of food processing on mango and emphasizes the available strategies for managing mango allergy.

Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice.

There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are "treated-to-target." For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a "master protocol" facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adoption would achieve greater collaboration and consistency in approaches to proactive management of food allergy in routine clinical practice. As a community, we need to actively pursue this with funders and established research collaborations to deliver the very best outcomes for our patients and their families.

Fish Allergy and Related Conditions in Children: A Review.

Fish allergy is the important food allergies in childhood, often persisting into adulthood. It can cause severe hypersensitivity reactions, including fatal anaphylaxis; furthermore, avoiding-fish diet has negative nutritional and psychological effects. Recent research studies focus on epitope structures and aim to develop sensitive and specific diagnostic tools, which have a better correlation with clinical reactions. Protocols with hypoallergenic parvalbumin or other recombinant antigens are also under study and will likely lead to new immunotherapy protocols. IgE-mediated fish allergy differs substantially from other forms of immunological adverse reactions to fish, such as Food Protein-Induced Enterocolitis Syndrome and eosinophilic esophagitis. In addition, fish ingestion can cause non-immunological adverse reactions, such as in the case of scombroid poisoning, anisakiasis and toxic poisoning. This review aims to summarize the characteristics of the main immunological and non-immunological fish reactions, analyzing the epidemiology, clinical manifestations, diagnosis and therapy, with a particular focus on clinical management.

Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome.

The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks.

What Is Alpha-Gal Syndrome?

This JAMA Patient Page describes alpha-gal syndrome, a type of food allergy to red meat products, and its symptoms, diagnosis, and treatment.

Effects of Early Diet on the Prevalence of Allergic Disease in Children: A Systematic Review and Meta-Analysis.

Recent evidence suggests that the timing of introduction, types, and amounts of complementary foods/allergenic foods may influence the risk of allergic disease. However, the evidence has not been updated and comprehensively synthesized. The Cochrane Library, EMBASE, Web of Science, and PubMed databases were searched from the inception of each database up to 31 May 2023 (articles prior to 2000 were excluded manually). Statistical analyses were performed using RevMan 5. The GRADE approach was followed to rate the certainty of evidence. Compared with >6 mo, early introduction of eggs (≤6 mo of age) might reduce the risk of food allergies in preschoolers aged <6 y (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.53, 0.81), but had no effect on asthma or atopic dermatitis (AD). Consumption of fish at 6-12 mo might reduce the risk of asthma in children (aged 5-17 y) compared with late introduction after 12 mo (OR, 0.61; 95% CI: 0.52, 0.72). Introduction of allergenic foods for ≤6 mo of age, compared with >6 mos, was a protective factor for the future risk (children aged ≤10 y) of AD (OR, 0.93; 95% CI: 0.89, 0.97). Probiotic intervention for infants at high risk of allergic disease significantly reduced the risk of food allergy at ages 0-3 y (OR, 0.72; 95% CI: 0.56, 0.94), asthma at 6-12 y (OR, 0.61; 95% CI: 0.41, 0.90), and AD at aged <6 y (3-6 y: OR, 0.70; 95% CI: 0.52, 0.94; 0-3 y: OR, 0.73; 95% CI: 0.59, 0.91). Early introduction of complementary foods or the high-dose vitamin D supplementation in infancy was not associated with the risk of developing food allergies, asthma, or AD during childhood. Early introduction to potential allergen foods for normal infants or probiotics for infants at high risk of allergies may protect against development of allergic disease. This study was registered at PROSPERO as CRD42022379264.

Long-term exposure from perinatal life to food-grade TiO2 alters intestinal homeostasis and predisposes to food allergy in young mice.

BACKGROUND: Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food-grade titanium dioxide (fg-TiO2 ), a common food additive. METHODS: Dams were fed a control versus fg-TiO2 -enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg-TiO2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time-point, using established models. Sensitization to CMP was investigated by measuring ß-lactoglobulin and casein-specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge. RESULTS: Perinatal exposure to fg-TiO2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism. CONCLUSIONS: Long-term perinatal exposure to fg-TiO2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect.

The Role of Biologics in the Treatment of Food Allergy.

The landscape of food allergy (FA) treatment is poised for a paradigm shift with the emergence of biologic therapies. The Food and Drug Administration approval of a standardized peanut powder for oral immunotherapy in 2020 marked a milestone, signaling a departure from allergen avoidance toward proactive treatment strategies. Although oral immunotherapy has been proven effective in desensitizing patients to specific allergens, there are several limitations such as lacking standardization, a long-time commitment to achieve maintenance, and adverse events. Biologics, including omalizumab, dupilumab, and antialarmins, have shown promise in treating various allergic diseases, including FA. These biologics target the underlying immunologic pathways driving allergic reactions, offering an antigen-agnostic approach. Omalizumab (anti-IgE) has been the most studied biologic in this space and can be used both as an adjunct therapy with oral immunotherapy and as monotherapy. Dupilumab targeting IL-4 and IL-13 also shows promise as an adjunct therapy. The emergence of antialarmins further broadens the spectrum of FA treatment possibilities. Biologics represent a transformative approach to FA treatment, directly addressing the underlying mechanisms. Future research should focus on patient selection criteria, personalized biomarker panels, optimal timing of intervention, and treatment durations.