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BACKGROUND: Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. METHODS: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. RESULTS: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. CONCLUSION: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.

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BACKGROUND: A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. METHODS: Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. RESULTS: Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). CONCLUSION: In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

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Allergen-specific IgE is a major mediator of allergic responses and contributes greatly to allergic disease in the human population. Therapies that inhibit the production of IgE would be useful for lessening the burden of allergic disease. A great deal of research has focused on how IgE responses are regulated, and several factors that promote the production of allergic IgE have been characterized. T follicular helper (TFH) cells expressing IL-4 are required for the development of IgE expressing B cells in the germinal center (GC). Ig somatic hypermutation and B cell selection in the GC leads to the development of high affinity allergen-specific IgE that promotes anaphylaxis, a severe form of allergic response. T follicular regulatory (TFR) cells are also found in the GC response and act with TFH cells in the selection of high affinity IgE + B cells. This review examines the current literature on IgE responses and TFR cells. In mouse studies, TFR cells have a suppressive role on IgE responses in allergic airway disease, however TFR cells also play a helper role in the IgE response in food allergy. In human studies, TFR cells correlate with a decreased allergic response but evidence for a direct suppressive role of TFR cells on IgE in vivo is lacking. TFR cells may represent a new target for allergy therapies, but caution must be exercised to promote the suppressor activity of TFR cells and not the helper activity of TFR cells on IgE responses.

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BACKGROUND: Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4+ T cells in children with IgE-mediated food allergies. METHODS: Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4+ T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4+ T cell differentiation was assessed by treating stimulated naïve CD4+ T cells from healthy volunteers with tacrolimus for 7 days. RESULTS: Egg allergic infants had impaired development of IFNγ+ Th1 cells and FoxP3+ transitional CD4+ T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4+ T cells from food allergic children after in vitro culture. SOCE of naïve CD4+ T cells was impaired in food allergic children. Naïve CD4+ T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression. CONCLUSIONS: In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.

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BACKGROUND: Eczema in early childhood is associated with the development of subsequent allergic diseases, including food allergy (FA), asthma and hay fever. However, eczema has a heterogenous presentation regarding onset age and persistence, which may lead to different allergic outcomes during childhood/adolescence. Recently, sub-phenotypes of eczema have been suggested as predictors of allergic multimorbidity. Thus, we aimed to identify associations of eczema phenotypes with FA, asthma and hay fever during childhood/adolescence. Additionally, we described the trajectories of eczema, asthma and hay fever stratified by FA presence. METHODS: TRACKER (Trajectories of Allergy in Children in Real Life Databases) is a population-based cohort study of 6852 children/adolescents from the Lifelines cohort. We investigated the associations of seven eczema phenotypes, based on onset age and persistence, with FA, asthma and hay fever using logistic regression, adjusted for appropriate covariates. Disease trajectories were determined by calculating prevalence at different ages. RESULTS: Participants who suffered from eczema throughout childhood showed higher risks of developing FA, hay fever and asthma. "Very early onset-persistent" eczema showed the strongest associations with FA, asthma and hay fever. The prevalence of eczema, asthma and hay fever at all ages was significantly higher in participants with FA, compared to those without. CONCLUSION: One of the largest cohort studies on this topic to date shows that (very) early onset and persistent eczema increases the risk of allergic multimorbidity. Identification of infants at risk for developing (very) early onset eczema is of utmost importance to prevent allergic multimorbidity.

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BACKGROUND: The basophil activation test (BAT) has been limited to research settings due to technical issues. Novel approaches using dry, ready-to-use reagents and streamlined protocols offer greater flexibility and may open opportunities for easier implementation in clinical research. OBJECTIVE: Using a streamlined BAT (sBAT) strategy and the settings of the baseline study of the EPITOPE trial of EPicutaneous ImmunoTherapy (EPIT™) for peanut allergy, we aimed to assess the feasibility of implementing BAT in a multicenter trial and to evaluate its utility in predicting the outcomes of peanut double-blind placebo-controlled food challenge (DBPCFC). METHODS: Whole blood samples were collected from subjects aged 1-3 years (n=241) undergoing baseline eligibility DBPCFC in the EPITOPE study across 15 clinical sites in North America. After preparation with sBAT reagents, processed samples were analyzed in a single central laboratory within 5 days of collection and preparation. The eliciting dose (ED) at DBPCFC was determined using PRACTALL criteria. Using a machine learning (ML) approach which incorporated BAT-derived features, clinical characteristics, and peanut-specific IgE, the ability to predict outcomes of interest (ED [<300 mg or >300 mg] and use of epinephrine) was assessed using data randomly split into training (n=182) and validation (n=59) subsets. RESULTS: The expression of basophil activation markers CD203c and CD63 correlated with ED and severity outcomes of DBPCFC. Most informative concentrations of peanut extract in the sBAT assay for these associations were 1 and 10 ng/ml. Using ML to assess the ability to predict the outcomes of DBPCFC, the best models using only the BAT-derived features provided relatively high sensitivities of 0.86 and 0.85 for predicting eliciting dose and epinephrine use, respectively, while specificities were lower, ranging from 0.60 to 0.80. While including specific IgE and SPT data in addition to those from sBAT did not improve the ability to identify individuals most at risk for severe reactions, it did improve the ability to identify patients with an eliciting dose above 300 mg. CONCLUSION: In addition to facilitating implementation in multicenter trials, sBAT retains the potential of BAT to characterize allergic patients and confirms its potential to contribute to predicting the outcome of oral food challenges.

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Food allergies and asthma significantly impact individual health and global healthcare systems. Despite established management protocols for asthma and the emerging use of oral immunotherapy for food allergy, adherence to treatments remains a challenge for healthcare professionals and patients. This review explores the differences in adherence required of asthma and food allergy treatments and strategies to improve adherence. We highlight the role of collaborative care coordination among healthcare professionals in enhancing adherence in asthma and food allergy management and improving patient outcomes.

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Soy-dependent exercise-induced anaphylaxis is likely underdiagnosed and potentially on the rise. As soy gains popularity in Western diets, we highlight it as a hidden allergen in a variety of processed foods, including those marketed toward exercise enthusiasts.

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The increasing prevalence of immune-mediated non-communicable chronic diseases, such as food allergies, has prompted a deeper investigation into the role of the gut microbiome in modulating immune responses. Here, we explore the complex interactions between commensal microbes and the host immune system, highlighting the critical role of gut bacteria in maintaining immune homeostasis. We examine how modern lifestyle practices and environmental factors have disrupted co-evolved host-microbe interactions and discuss how changes in microbiome composition impact epithelial barrier function, responses to food allergens, and susceptibility to allergic diseases. Finally, we examine the potential of bioengineered microbiome-based therapies, and live biotherapeutic products, for reestablishing immune homeostasis to prevent or treat food allergies.

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The early development of the neonatal immune system is profoundly influenced by exposure to dietary and microbial antigens, which shapes mucosal tolerance. Successful oral tolerance induction is crucially dependent on microbially imprinted immune cells, most notably the RORγt+ regulatory T (Treg) and antigen presenting cells and is essential for preventing food allergy (FA). The development of FA can be envisioned to result from disruptions at key checkpoints (CKPTs) that govern oral tolerance induction. These include gut epithelial sensory and effector circuits that when dysregulated promote pro-allergic gut dysbiosis. They also include microbially imprinted immune regulatory circuits that are disrupted by dysbiosis and pro-allergic immune responses unleashed by the dysregulation of the aforementioned cascades. Understanding these checkpoints is essential for developing therapeutic strategies to restore immune homeostasis in FA.

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The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children's Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow's-milk-free diet.

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Avoidant/Restrictive Food Intake Disorder (ARFID) and food neophobia present significant challenges in pediatric healthcare, particularly among children with food allergies (FAs). These eating disorders, characterized by the persistent avoidance or restriction of food, can lead to severe nutritional deficiencies and psychosocial impairments. The presence of FAs further complicates these eating behaviors, as the fear of allergic reactions exacerbates avoidance and restrictive patterns. This comprehensive review synthesizes current knowledge on ARFID and food neophobia, focusing on their definitions, characteristics, and the unique challenges they present in the context of FAs. The review explores the critical role of healthcare professionals, especially nurses, in integrating psychological and clinical care to improve outcomes for affected children. A multidisciplinary approach, including Cognitive Behavioral Therapy (CBT) and Family-Based Therapy (FBT), is emphasized as essential in addressing the complex needs of these patients. The review also highlights the need for standardized treatment protocols and further research on the long-term outcomes of these disorders, aiming to enhance therapeutic strategies and family support systems. Effective management of ARFID and food neophobia in the context of FAs requires a holistic and integrated approach to mitigate the profound impacts on a child's growth, development, and overall well-being.

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The specific detection of serum IgE antibodies specific to allergens (sIgE Abs) that can crosslink the plural high-affinity IgE receptor (FcεRIα) molecules on the surface of mast cells or basophils with a multivalent allergen can reduce the false-positive diagnoses observed in chemiluminescent and fluorescence enzyme immunoassays for type-I allergic patients. In this study, we detected sIgE Abs to the egg-allergen ovalbumin (OVA) and the wheat-allergen gluten in the sera of rats sensitized with each allergen using an amplified luminescence proximity homogeneous assay by crosslinking (AlphaCL). OVA and gluten were reacted with each sIgE Ab in the sera. Then, acceptor and donor beads labeled with the human FcεRIα were added to the reacted solution. The luminescence intensity for anti-OVA IgE Abs in the sera with the removal of IgG Abs was observed in five of seven (71.4%) of the sensitized rats, whereas no signals were observed in any of the unsensitized rats. The AlphaCL could also detect anti-gluten sIgE Abs in the sera of sensitized rats, but not of unsensitized rats. In conclusion, we successfully detected sIgE Abs in the sera of rats sensitized to two allergens using the AlphaCL. This detection method has the potential to be used as a new diagnostic tool for type-I allergic patients.

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Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies.

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Atopic diseases, including atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) are closely related to inflammatory diseases involving different body sites (i.e. the skin, airway, and digestive tract) with characteristic features including specific IgE to allergens (so-called 'atopy') and Th2 cell-mediated inflammation. It has been recognized that AD often precedes the development of other atopic diseases. The progression from AD during infancy to FA or asthma/AR in later childhood is referred as the 'atopic march' (AM). Clinical, genetic and experimental studies have provided evidence that allergen sensitization occurring through AD skin could be the origin of the AM. Here, we provide an updated review focusing on the role of the skin in the AM, from genetic mutations and environmental factors associated with epidermal barrier dysfunction in AD and the AM, to immunological mechanisms for skin sensitization, particularly recent progress on the function of key cytokines produced by epidermal keratinocytes or by immune cells infiltrating the skin during AD. We also highlight the importance of developing strategies that target AD skin to prevent and attenuate the AM.

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The prevalence of allergies has been globally escalating. While allergies could appear at any age, they often develop in early life. However, the significant knowledge gap in the field is the mechanisms by which allergies affect certain people but not others. Investigating early factors and events in neonatal life that have a lasting impact on determining the susceptibilities of children to develop allergies is a significant area of the investigation as it promotes the understanding of neonatal immune system that mediates tolerance versus allergies. This review focuses on the research over the recent 10 years regarding the potential maternal factors that influence offspring allergies with a view to food allergy, a potentially life-threatening cause of anaphylaxis. The role of breast milk, maternal diet, maternal antibodies, and microbiota that have been suggested as key maternal factors regulating offspring allergies are discussed here. We also suggest future research area to expand our knowledge of maternal-offspring interactions on the pathogenesis of food allergy.

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ETHNOPHARMACOLOGICAL RELEVANCE: Food allergies have increasingly become a disease that affects global health and need for corresponding therapeutic drugs urgently. As a traditional Chinses medicine with a wide range of pharmacological effects, however, there was no clear research confirming therapeutic effect and pharmacological substances of Corydalis yanhusuo (YHS) on food allergies. Mast cells (MCs) are the main effector cells which mediate allergic and pseudo-allergic reactions. MATERIALS AND METHODS: In this study, we investigated the effect of YHS extract on treating food allergy and its underlying mechanism. The inhibitory effect of YHS on MCs activation in vitro was evaluated by Ca2+ influx, degranulation, and cytokine release detection. The in vivo effect was investigated using the passive cutaneous anaphylaxis (PCA), active systemic allergy as well as OVA-induced food allergy mice. Western blot was performed to reveal the signaling pathway. RESULTS: YHS extract showed an inhibitory effect on MCs activation and food allergy both in vitro and in vivo. PLC/PKC/STAT3 signaling pathway was suppressed by YHS extract in the disease. HPLC analysis revealed YHS extract contains corydaline and tetrahydropalmatine, and both compounds inhibited MCs activation induced by C48/80 in vitro. CONCLUSION: YHS extract inhibited the MCs activation and food allergy via PLC/PKC/STAT3 pathway.