The External Exposome and Food Allergy: How Environmental Exposures Shape Disease Risk

ABSTRACT

IgE‐mediated food allergy is a global health issue with rising prevalence that cannot be explained by genetic change alone, strongly suggesting that environmental exposures are a key driver. The external exposome encompasses several exposures that influence the developing immune system and modify food allergy risk. Environmental exposure to food allergens in household dust is increasingly recognized as a risk factor for sensitization, whereas early oral introduction promotes tolerance. Early‐life microbial exposures, especially those associated with rural and farming environments, may protect against food allergies by stimulating innate immune pathways and shaping the gut microbiome. Co‐exposures to microbial adjuvants can further alter risk in a timing‐dependent manner. Epidemiological birth cohort studies have linked exposure to air pollutants, such as particulate matter and nitrogen dioxide, to food sensitization and allergy. Synthetic chemicals represent an emerging risk factor by disrupting epithelial barrier integrity and immune regulation. Ultra‐processed food consumption and dietary additives may further increase risk by altering gut permeability and immune function. Significant gaps remain in our understanding of the most relevant environmental exposures affecting food allergy risk. Future research using longitudinal cohort designs and exposome‐wide approaches is essential for developing evidence‐based strategies to prevent food allergy.

1. Introduction

IgE‐mediated food allergy is a potentially life‐threatening condition that has emerged as a global health concern, affecting up to 10% of children and adults in some populations [1, 2]. Epidemiological data suggest that food allergy prevalence has risen substantially over the past few decades, particularly in developed countries [1, 3]. The increasing food allergy rates cannot be attributed to genetic shifts alone, indicating that environmental changes are likely responsible for the food allergy epidemic [4, 5, 6]. From conception onward, individuals encounter a broad array of environmental exposures that can shape immune system development and modify the risk of allergic disease [7, 8]. Collectively, these nongenetic influences are referred to as the external exposome, which encompasses diet, pollution, chemicals, microbes, allergens, and other environmental and social factors [9, 10].

This narrative review provides a critical evaluation of current evidence on the role of the external exposome in food allergy, with a particular focus on how exposures to environmental foods, microbes, synthetic chemicals, food additives, and air pollution contribute to the development of food allergy, highlighting where evidence is well established versus preliminary. Since our earlier reviews on this topic [4, 5], new evidence has emerged across each of these domains, including birth cohort data linking air pollution to challenge‐proven peanut allergy [11], reports of farm exposure associated with immune activation and lower food allergy incidence in early life [12], and largely preclinical studies on how synthetic chemicals and dietary additives can impact immune responses to foods [13, 14, 15]. Together, these advances provide new insights into how co‐exposures to foods and environmental agents during critical windows of immune development determine sensitization versus tolerance (Box 1). This review draws on PubMed literature searches for each exposure domain supplemented by author expertise. The scope was intentionally limited to environmental exposures that shape food allergy risk rather than the diagnosis and management of established disease, which are addressed by recent EAACI guidelines [16].

BOX 1. Major milestone discoveries.

• Riedler et al. (2001) [60]: Cross‐sectional study showing that exposure to a farming environment during the first year of life protected against the development of asthma and atopic sensitization, establishing the importance of early‐life exposures on immune development.

• Lack et al. (2003) [159]: Case–control study reporting that peanut allergy was associated with eczema and topical exposure to peanut‐containing oils, which became the conceptual foundation for the dual‐allergen exposure hypothesis.

• Brough et al. (2013, 2014) [25, 28]: These population‐based cohort studies established that biologically active peanut protein was distributed in dust throughout the homes, and that early‐life environmental peanut exposure was associated with increased risk for peanut sensitization in children with filaggrin loss‐of‐function mutations, supporting the hypothesis that epicutaneous peanut sensitization occurs through an impaired skin barrier.

• Du Toit et al. (2015) [44]: Landmark clinical study demonstrating that early dietary peanut introduction in high‐risk infants reduced the relative risk of peanut allergy by 81%. This study and the follow‐up LEAP‐On trial (Du Toit et al. 2016) demonstrated that early peanut consumption was an effective strategy for preventing peanut allergy in children.

• Chassaing et al. (2015) [138]: Foundational study showing that low concentrations of two ubiquitous emulsifiers induced host–microbiota perturbations and gut inflammation in mice, providing evidence that dietary emulsifiers could disrupt gut barrier function, which is essential for tolerance to microbes and foods.

• Stein et al. (2016) [58]: Cohort study showing that Amish children (traditional farming) had sixfold lower rates of allergic sensitization than Hutterite children (industrial farming), providing further evidence that early‐life farming exposure is protective against atopic diseases.

• Abdel‐Gadir et al. (2019) [65]: This study identified a Treg/MyD88/RORγt pathway through which commensal bacteria suppress food allergy in mice, providing mechanistic insights into how the microbiome directs tolerance to foods.

• Akdis (2021) [101]: Landmark review describing the “epithelial barrier hypothesis,” which proposes that increasing exposure to epithelial‐damaging agents linked to modernization and urban living underlies the increasing prevalence of allergic and other noncommunicable diseases.

• Kulis et al. (2021) [33]: This rostrum expanded upon the dual‐allergen exposure hypothesis, presenting evidence from murine models and human cell‐based studies that support the airway as an alternative route of food sensitization.

• Lopez et al. (2024) [11]: First study to link PM_2.5 and NO₂ exposure to oral food challenge‐confirmed peanut allergy in a birth cohort. Preclinical animal studies conducted in the same year by Immormino et al. [36] showed that PM acts as an adjuvant to promote peanut allergy, providing a mechanistic explanation for how air pollution could be a risk factor for food sensitization.

• Jackson et al. (2025) [12]: Longitudinal birth cohort study finding that Old Order Mennonite infants exposed to a traditional farming lifestyle had earlier maturation of B cell immunity and lower egg allergy incidence compared to urban/suburban infants.

2. Environmental Food Exposures

Environmental exposure to food allergens via non‐oral routes is increasingly recognized as a risk factor for developing food allergies, challenging the traditional paradigm that allergic sensitization to foods occurs through the gastrointestinal tract [17, 18]. Environmental food exposure refers to the presence of residual allergens on surfaces, in settled dust, and occasionally in the air. This is distinct from cross‐contact, which describes the inadvertent transfer of allergens between foods or surfaces during preparation. While cross‐contact is most relevant to triggering reactions in allergic individuals, environmental food exposures are increasingly implicated in sensitization (i.e., the production of food‐specific IgE) [17, 19].

Food allergens, including peanuts, eggs, milk, and fish, have been detected in a wide range of indoor environments, including homes, nurseries, schools, and clinical settings [20, 21, 22]. Household dust is a major source of exposure, with food proteins detected in nearly all homes at levels exceeding those of typical indoor allergens, such as house dust mites [23]. A recent study using a novel ambient air sampling device detected multiple food allergens—including peanut, milk, and egg—in homes across the United Kingdom and the United States, indicating that food allergens can also be airborne in the living environment [24]. Previous work by Brough et al. [25] demonstrated that biologically active peanut protein is widely distributed throughout the home, including infant sleep and play areas, with a strong correlation between household peanut consumption and environmental levels of peanut in dust. However, food allergens remain detectable in homes and classrooms where those foods are excluded, reflecting that they are readily disseminated throughout the living environment [22, 26]. Although cleaning reduces allergen levels, complete eradication is rarely achieved, resulting in persistent low‐dose exposure, particularly on surfaces made with porous materials [20].

The dual allergen exposure hypothesis (Figure 1) proposes that early cutaneous exposure leads to sensitization, whereas oral exposure promotes tolerance [27]. Infants, particularly those with atopic dermatitis, have an impaired skin barrier that facilitates allergen penetration and interaction with immune cells [27]. Epidemiological studies demonstrate a strong association between eczema and peanut sensitization, with an increased risk in children with filaggrin loss‐of‐function mutations [28]. Brough et al. [29, 30] demonstrated a dose–response relationship between environmental exposure to peanuts in household dust and peanut sensitization, particularly among children with skin barrier dysfunction due to eczema. Evidence that environmental exposure to foods other than peanuts is a risk factor for sensitization is more limited. A cross‐sectional study of 159 children in Japan found no association between egg protein levels in house dust and self‐reported egg allergy at 6 years of age [31]. A recent case–control study found that hazelnut and sesame protein levels were higher in dust samples from the homes of patients with newly physician‐diagnosed allergies than in nonallergic controls, suggesting a potential role for environmental exposure, although prospective studies are needed to verify this [32]. In addition to the skin, the respiratory tract is also a plausible route for allergic food sensitization [33]. As noted above, food allergens can be airborne in homes and thus inhaled [24]. Mouse models show that airway exposure to peanut results in sensitization, which can occur at very low allergen levels (ng quantities) when mice are co‐exposed to environmental adjuvants, such as house dust or pollutants [34, 35, 36, 37]. In humans, pathogenic peanut‐specific CD4⁺ T cells express both skin‐ and lung‐homing receptors, suggesting they are primed at both sites [38]. Taken together, these studies support a multi‐route model of sensitization to environmental foods.

FIGURE 1.

The route of exposure to foods is an important determinant of allergy versus tolerance. Environmental food allergens are ubiquitous in the living environment. Non‐oral exposure to environmental food allergens through an impaired skin barrier, such as in patients with atopic dermatitis, or through the airways, can activate conventional dendritic cells (cDCs), which in turn drive the differentiation of T follicular helper cells (Tfh), which can direct B cells to produce allergen‐specific IgE, resulting in food sensitization and allergy. Co‐exposure to environmental adjuvants, such as microbial products in house dust and particulate air pollutants, may further increase the risk of sensitization to environmental foods, particularly with airway exposure. In contrast, oral exposure to foods results in immunological tolerance, likely mediated by tolerogenic DCs that express the transcription factor RORγt and regulatory T cells (Tregs). Oral exposure also promotes IgG4 and possibly IgA responses to foods, which further mediate tolerance to ingested antigens. The concept that oral and non‐oral food exposures result in tolerance or allergy, respectively, is referred to as the dual‐allergen exposure hypothesis. Created with BioRender.com.

In contrast to cutaneous and airway exposures, oral exposure promotes immune tolerance through mechanisms that involve the development of regulatory T cells (Tregs) and the production of food‐specific IgG4 and possibly IgA [39, 40]. Recent studies have identified dendritic cells (DCs) expressing the transcription factor RORγt as critical for inducing oral tolerance in mice, and evidence suggests that this DC subset also exists in human gut and lymphoid tissues [41, 42, 43]. Clinical trials, including the LEAP study and its long‐term follow‐up studies, demonstrate that early dietary peanut introduction significantly reduces the risk of peanut allergy in high‐risk infants and confers sustained tolerance into adolescence [44, 45, 46]. Furthermore, recent data from the LEAP‐Trio cohort suggest that environmental peanut exposure through non‐oral routes may increase risk: younger siblings of LEAP participants were more likely to develop peanut allergy unless oral consumption also occurred, reinforcing the importance of early ingestion in promoting tolerance, particularly in the context of high environmental peanut exposure [47]. A recent meta‐analysis also found evidence that early dietary introduction of eggs protects against egg allergy, but evidence that early dietary introduction of milk or other food allergens is protective was less certain [48].

Overall, the evidence for environmental peanut exposure as a risk factor for sensitization is comparatively strong, whereas evidence for other food allergens remains limited to small cross‐sectional studies. Therefore, more studies are needed to determine if environmental exposure to foods other than peanut is a risk factor for food sensitization and whether early dietary exposure can mitigate this risk.

3. Microbial Exposures

Early‐life microbial exposures play an important role in shaping immune system development and the gut microbiome composition, thereby influencing whether exposure to foreign antigens, including food proteins, results in tolerance or allergy (Figure 2) [49]. Epidemiological studies have consistently shown that rural and farming environments confer protection against atopic diseases, likely through richer and more diverse early‐life microbial exposures [50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60]. In contrast, urbanization and the modern lifestyle decrease the breadth of microbial exposures during early life, which may be linked to the rising prevalence of atopic disease [61, 62].

FIGURE 2.

Early‐life environmental exposures can modulate food allergy risk by altering the microbiome and immune system. Certain environmental exposures have been associated with protection against allergic sensitization, including a rural or farming lifestyle, pets within the home, or having older siblings. These exposures are associated with increased Bifidobacterium colonization in the gut, microbiome diversity, maturation of the gut microbiome, and the production of short‐chain fatty acids (SCFAs) that promote oral tolerance. They also activate the innate immune system, increase systemic IgG4 and mucosal IgA responses, and promote Th1 and Treg development. In contrast, harmful environmental exposures, such as an urban/modern lifestyle or antibiotic exposure, can deplete Bifidobacterium species in the gut microbiome and reduce microbiome diversity, leading to dysbiosis. These detrimental exposures are associated with increased Th2 priming, IgE class switching, and impaired Treg function, leading to disruption of immune tolerance to foods. Created with BioRender.com.

Microbial exposures can shape immune development by activating innate signaling molecules, including Toll‐like receptors (TLRs), resulting in a shift toward Th1 and regulatory responses to allergens [63]. A recent study found significant differences in peripheral blood mononuclear cell gene expression in TLR and innate cytokine signaling pathways between South African children in rural and urban settings [64]. Mouse studies show that certain commensal bacteria activate Tregs via a MyD88/RORγt pathway to suppress food allergy [65]. Microbial exposures can also stimulate protective humoral and mucosal immune responses. In a birth cohort study of Old Order Mennonite (OOM) children, exposure to a traditional farming lifestyle led to early B cell maturation, characterized by increased systemic IgG4 and mucosal IgA production, which was associated with a lower incidence of egg allergy than in urban and suburban children [12]. Microbes can also affect immune responses to foods indirectly by metabolizing allergens. A recent study found that human saliva and jejunum contain peanut‐degrading bacteria, which inhibited IgE‐mediated anaphylaxis when transferred to mice [66]. These studies highlight the importance of microbes in promoting immune tolerance to foods.

Exposure to microbes within the living environment is likely an important factor in allergic sensitization. The indoor environment is rich in bacteria and fungi [67], which can affect the immune system during the perinatal period and influence the risk of developing allergies in later childhood [68, 69]. Differences in the composition of the indoor microbiome are evident between the homes of urban and rural children and may influence the later risk of allergic disease [50, 56]. Analysis of microbes in bed dust collected from 514 infants in the COPSAC₂₀₁₀ cohort found that bacterial and fungal genera enriched in rural homes were associated with reduced risk for atopic disease, although food allergy was not specifically evaluated [50]. The presence of pets in the home also affects the composition of the indoor microbiome, which may partly explain why living with a dog is associated with reduced odds of childhood food sensitization and allergy [70, 71, 72, 73].

Early‐life microbial exposures help inform the composition of the gut microbiome [56, 74, 75], which plays a critical role in regulating tolerance to dietary antigens by releasing short‐chain fatty acids and inducing regulatory T cells [76]. Mouse models have shown that exposure to microbes in house dust can alter the gut microbiome, resulting in reduced Th2 responses and protection from allergen‐induced airway inflammation [77]. Farm and animal exposure have particularly strong effects on gut microbiome composition. Growing up on a farm was associated with a higher ratio of anaerobic to facultative bacteria at 1 week of age, which negatively correlated with subsequent allergy diagnosis [78]. Specifically, prenatal and perinatal timing of farming exposures, such as farm animals and consumption of unpasteurized farm milk, are associated with protection against infant atopic sensitization [58, 60, 79, 80, 81]. Pet ownership also influences gut microbiome development in infants, leading to increased abundance of bacteria that are negatively associated with childhood atopy [78, 82]. Interestingly, a recent report from the Canadian CHILD Cohort Study found that pet exposure altered the gut microbiome in ways that corresponded to host genotypes, indicating that gene‐by‐environment interactions are important in determining how exposures affect gut microbiome composition [83]. Moreover, the protective effect of older siblings against food allergies is likely due to environment‐mediated changes in the gut microbiome. In an Australian birth cohort, having older siblings accelerated gut microbiota maturation in infants, which was associated with decreased odds of physician‐diagnosed food allergy (OR 0.45, 95% CI 0.33–0.61) at 12 months of age [84]. A recent meta‐analysis of 190 studies involving 2.8 million participants found that antibiotic exposure and cesarean delivery, which reduce microbial diversity and promote dysbiosis, are risk factors for food allergy [85]. Indeed, children from the previously mentioned OOM cohort, who live on traditional farms and have low rates of food allergies, high rates of vaginal home birth, low rates of perinatal antibiotic use, and large families [86], have a gut microbiome enriched for Bifidobacterium longum species, which may promote oral tolerance to allergens [54, 87]. Furthermore, a recent Japanese birth cohort study found that children with Bifidobacterium‐dominant gut microbiomes had a lower risk of developing food sensitization and physician‐diagnosed food allergies than those with Bacteroides‐ or Klebsiella‐dominant microbiomes [88].

Indoor microbes are also a source of environmental adjuvants, including endotoxin, proteases, and other pathogen‐associated molecules with immunostimulatory properties [89]. In mouse models, co‐exposure to environmental adjuvants in house dust and to peanut allergen results in peanut sensitization and the development of allergy through a MyD88‐dependent pathway [34, 35]. The timing of microbial exposures relative to allergen is likely an important factor, as mice exposed to endotoxin and other microbial products before allergen exposure are protected from allergic sensitization [35, 90]. This may partly explain why studies have shown that house dust endotoxin levels have been associated with both decreased and increased risk of food sensitization in children [91, 92], and highlights the importance of considering co‐exposures to environmental food allergens when assessing the impact of microbial exposures on the development of food allergies.

Although the hygiene hypothesis posits that exposure to pathogenic microbes would protect against atopy, some studies have found that early‐life infections may be associated with increased risk for asthma and allergic diseases. Recent meta‐analyses have found that infections during pregnancy and infancy are associated with increased risk for asthma and allergic rhinitis [93, 94]. However, the role of infections in the development of food allergies is less clear. Mouse models have shown that gut pathogens can act as adjuvants for immune responses against a dietary antigen [95], but evidence that enteric infections increase the risk for food sensitization in children is lacking [96]. Individuals who experienced frequent respiratory viral infections during early childhood and were seropositive to cytomegalovirus by age 2 years had a higher prevalence of aeroallergen and food sensitization at age 20 years [95]. Interestingly, children born during the first weeks of the SARS‐CoV‐2 (COVID‐19) lockdown had lower rates of food sensitization and allergy than those born pre‐pandemic, a pattern that coincided with decreased rates of viral respiratory infections [97]. However, it is likely that lower rates of antibiotic use and changes in feeding practices during the lockdown also contributed to the decreased food allergy prevalence in this population.

In summary, there is relatively strong evidence from multiple cohort studies linking farm/rural environments and gut microbiome maturation to reduced food allergy risk, whereas the role of specific microbial adjuvants in modifying food allergy risk is primarily limited to preclinical models and observational studies. More studies are needed to determine whether the protective effects of early‐life microbial exposures can be harnessed therapeutically to prevent and treat food allergies.

4. Air Pollution Exposures

Air pollution poses a serious public health threat worldwide, with 90% of the global population living in areas that fail to meet adequate air quality standards [98]. Inhalable pollutants, such as particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM_2.5) or ≤ 10 μm (PM₁₀), ozone, sulfur dioxide, and nitrogen dioxide (NO₂), are a significant cause of morbidity and mortality, being responsible for an estimated 6.7 million deaths worldwide in 2019 [99]. Children bear a disproportionate burden of air pollution's health consequences, particularly those from low‐income communities and certain racial and ethnic groups [100]. In addition to its negative effects on cardiovascular and respiratory health, exposure to air pollution is also a risk factor for asthma and other allergic diseases [98]. Air pollutants can damage epithelial cells in the skin and mucosal surfaces, leading to the release of alarmins that promote Th2 polarization and allergic sensitization, a concept known as the “epithelial barrier hypothesis.” [101] Prenatal exposure to ambient air pollution may further reshape early‐life immune responses in mucosal tissues, increasing the risk of allergic sensitization in later childhood [102].

In addition to its well‐established role in asthma and allergic respiratory disease [103], there is growing evidence that air pollution may also contribute to the development of food allergies. The PIAMA birth cohort study in the Netherlands found positive associations between traffic‐related air pollutant exposure (PM_2.5, NO₂) and food sensitization at 4 years of age and, among previously non‐sensitized individuals, at 8 years of age [104, 105]. A more recent analysis of the PIAMA birth cohort found that exposure to PM_2.5, PM₁₀, and NO₂, but not ultrafine PM, was associated with food sensitization through age 16 years [106]. The Swedish BAMSE birth cohort study also found that exposure to PM₁₀ and nitrogen oxides was associated with food sensitization at 8 years of age, but not at 4 years of age [107, 108]. More recently, a Chinese cohort study of 2588 preschool children found the prevalence of self‐reported food allergy was associated with prenatal (adjusted [a] OR 1.24, 95% CI 1.00–1.54) and postnatal (aOR 1.38, 95% CI 1.03–1.85) exposure to NO₂ [109]. In another retrospective study involving over 20,000 families across five cities in China, NO₂ exposure during the first trimester was associated with self‐reported food allergy, whereas PM₁₀ and ozone exposures were identified as postnatal risk factors in multi‐pollutant models [110]. A limitation of these studies is that the endpoints of food sensitization or self‐reported diagnoses of food allergies are not equivalent to clinically verified food allergies. Addressing this limitation, Lopez et al. [11] recently investigated the association between air pollution and challenge‐proven food allergies using data from the Australian HealthNuts birth cohort study. They found that high NO₂ exposure at age 1 year was associated with higher peanut allergy prevalence at ages 1 (aOR 2.21, 95% CI 1.40–3.48) and 4 (aOR 2.29, 95% CI 1.28–4.11) years. Likewise, increased PM_2.5 exposure at age 1 year was associated with peanut allergy at ages 4, 6, and 10 years. Interestingly, neither pollutant was associated with the prevalence of egg allergy. A recent meta‐analysis of 21 studies with 120,454 participants revealed that the association between PM_2.5 and food allergy was significant only in developed countries (OR 1.34, 95% CI 1.16–1.55), suggesting that certain environmental exposures in less‐developed countries may mitigate the risk of air pollution on the development of food allergy [111]. Mouse studies have shown that co‐exposure to PM (diesel exhaust) and peanut allergen leads to peanut allergy by inducing allergen‐specific T follicular helper cells through an IL‐1‐dependent pathway [36], providing a possible mechanism for how air pollutant exposure is a risk factor for food allergies.

Given that children spend nearly 90% of their time indoors, indoor air quality is also likely to impact the development and severity of allergic diseases [112]. In addition to outdoor pollutants that penetrate the home envelope, indoor air pollutants include PM and NO₂ from cooking and heating, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons, tobacco smoke, and mold [112, 113]. In a recent Chinese retrospective cohort study involving 8689 preschoolers, dampness, new furniture (a source of VOCs), and environmental tobacco smoke exposure during pregnancy and infancy were associated with self‐reported food allergy [114]. Household factors that affect indoor air quality, including plastic toys and summer air conditioning, were also associated with self‐reported food allergy in a retrospective cohort study in China [110]. In the previously mentioned meta‐analysis, exposure to indoor mold and dampness was a risk factor for self‐reported food allergies (OR 1.55, 95% CI 1.23–1.95) [111]. Most evidence that indoor air pollution is a risk factor for food allergies comes from Chinese cohort studies; therefore, the generalizability of these findings to other populations remains to be determined.

Overall, birth cohort studies increasingly support an association between air pollutants and food sensitization and food allergies, although most evidence is limited to a small number of studies and geographic regions. While animal studies have provided mechanistic evidence supporting a causal role for specific air pollutants in food allergies, more research is needed to translate these findings to humans.

5. Chemical Exposures

In addition to changes in microbial exposures, our modern lifestyles are also characterized by increased exposure to synthetic chemicals. It is estimated that over 350,000 chemicals have been introduced to the human exposome over the past six decades, including phthalates, bisphenols, per‐ and polyfluoroalkyl substances (PFAS), pesticides, detergents, and other cleaning products [6]. The full impact of these chemical exposures on human health is incompletely understood, as less than 5% of synthetic chemicals have been adequately studied [115]. Many synthetic chemicals have been shown to affect the immune system, thereby modifying the risk of developing allergic diseases [4, 116].

The indoor chemical exposome includes numerous endocrine‐disrupting chemicals, including polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), PFAS, microplastics, and plasticizers such as phthalates and bisphenols [117]. Although PCBs were banned in the United States in 1979 and BFRs in 2013, they persist in the environment and remain in our food supply and, ultimately, in human blood [118]. In the French EDEN mother–child cohort, early‐life dietary exposure to PCBs and BFRs was associated with an increased risk of a multimorbidity allergic disease cluster (including food allergies, eczema, asthma, and allergic rhinitis), although food allergy was not evaluated as an isolated outcome [119]. Microplastics and plasticizers are also ubiquitous in the environment and lead to adverse health outcomes [120]. Emerging evidence suggests that microplastics and nanoplastics may contribute to the development of IgE‐mediated food allergy. In a mouse model of food allergy, orally delivered nanoplastics exacerbated allergic symptoms, increased gut barrier permeability, and promoted dysbiosis of the microbiome [121]. Other studies have demonstrated that microplastics and nanoplastics can bind to food allergens within a food matrix and alter their tertiary structure, potentially decreasing their digestibility [122, 123]. Human intestinal epithelial cell cultures treated with polyethylene terephthalate microplastics exhibited impaired barrier integrity and disrupted cellular homeostasis [124]. In a Chinese population study involving 400 children, phthalate exposure was associated with higher total IgE levels and an increased risk of food sensitization [125]. Mouse models have shown that exposure to di(2‐ethylhexyl) phthalate (DEHP) exacerbates food allergic responses [126]. Prenatal and postnatal exposures to bisphenols can have multiple effects on the gut and immune system, including increasing intestinal permeability [127], altering the gut microbiome [128], and decreasing T regulatory cells [129], all of which play a role in the development of food allergy. However, epidemiological studies are mixed on the role of bisphenol A (BPA) in food allergies. In a multicenter birth cohort, Gaylord et al. [130] found that prenatal BPA exposure was associated with both decreased and increased rates of childhood self‐reported food allergies, depending on the timing of exposure and the child's sex.

Many household and personal care products contain detergents, including cleaning products, dish soap, degreaser, laundry detergent, fabric softeners, toothpaste, shampoo, and body wash [131]. Sodium lauryl sulfate (SLS, also known as sodium dodecyl sulfate, SDS) is a surfactant used in many of these products and can be either ingested or come into prolonged contact with skin [131]. Regardless of the route of exposure, detergents can impair the epithelial barrier by disrupting the lipid layer and tight junctions between cells, thereby increasing exposure to allergens and other toxicants [131]. One study demonstrated that a rinse aid diluted to 1:20,000 disrupted the gut epithelial barrier, indicating that even at low doses, detergents can exert potent biological activity [13]. Furthermore, low‐dose detergents have also been shown to disrupt tight junctions in human bronchial epithelial and skin epidermal cells, demonstrating that these disruptive properties affect multiple epithelial surfaces [132, 133]. Disruption in the epithelial barrier leads to the release of alarmins, including IL‐33, TSLP, and IL‐25, which direct the immune system toward a Th2 response [134]. Treating esophageal cells and organoids with SLS disrupted barrier integrity and increased IL‐33 levels, suggesting that detergent exposure may contribute to the development of eosinophilic esophagitis [135]. Overall, emerging evidence suggests that repeated exposure to detergents in early life may be a risk factor for the development of allergic disease.

Taken together, the evidence for synthetic chemicals and detergents as risk factors for food allergies remains largely preclinical or based on small human studies. Well‐designed prospective cohort studies are needed to define how chemical exposures impact the developing immune system and modify allergy risk.

6. Dietary Exposures

There has been growing scrutiny of how dietary changes over the past few decades may be contributing to the development of food allergies. The increasing prevalence of food allergies has paralleled a shift in Western diets characterized by reduced dietary fiber intake and increased consumption of ultra‐processed foods (UPFs), which contain additives such as emulsifiers and preservatives to prolong shelf life [136]. While establishing a causal relationship between the modern diet and the food allergy epidemic is challenging, recent preclinical studies are providing mechanistic insights into how food processing and additives may affect intestinal barrier integrity, immune cell function, and gut microbiome composition—all critical factors for oral tolerance [137].

A recent systematic review by the EAACI task force found that maternal and childhood dietary exposure to UPFs is associated with childhood food allergies [136]. UPFs often contain emulsifiers, added sugars, refined carbohydrates, added salt, and saturated fats, which are associated with adverse health outcomes [137]. Emulsifiers are detergent‐like molecules used in many processed foods to blend and stabilize ingredients that might otherwise separate, thereby improving the taste, texture, and consistency of the resulting product. However, emulsifiers have been linked to gut barrier dysfunction and inflammation, which could facilitate food allergy development. Mouse models show that common dietary emulsifiers disrupt normal host–microbiota interactions, resulting in gut inflammation [138]. Recently, two widely used emulsifiers, polysorbates 20 and 80, were shown to disrupt epithelial barrier function and induce secretion of pro‐inflammatory cytokines in human intestinal organoids [139]. Moreover, carrageenan food emulsifiers were shown to disrupt intestinal barrier integrity and induce a pro‐inflammatory transcriptional response using a gut‐on‐chip model [140]. A common byproduct of food processing is the formation of advanced glycation end‐products (AGEs), resulting from the nonenzymatic combination of proteins with sugars during high‐heat cooking, with immunologic consequences [141]. AGEs can have adverse effects on human epithelial and immune cells, including alterations of the gut barrier, increased transepithelial passage of food allergens, and stimulation of Th2 cytokine production by PBMCs from allergic children [142]. Long‐term dietary intake of AGEs increased susceptibility to experimental food allergy in mice, which was mediated by crosstalk between the receptor for AGE (RAGE) and TLR4 [14]. Analysis of data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010 showed that consumption of AGE‐containing UPFs was positively associated with self‐reported food allergy [14]. Moreover, pediatric patients with physician‐diagnosed food allergies had higher dietary AGE intake and higher skin AGE levels than age‐matched controls, supporting a potential role for AGEs in facilitating the development of food allergies [142]. Artificial sweeteners, such as aspartame and sucralose, are commonly used in UPFs and are also associated with gut barrier disruption, enhanced allergic symptoms, and impaired oral tolerance [143, 144, 145]. Another ubiquitous food additive, silicon dioxide, prevented oral tolerance in a mouse model [15]. Taken together, these studies provide a rationale for limiting UPF consumption as a strategy to mitigate the risk of developing food allergies.

Dietary nutrient intake, especially during pregnancy, is known to influence offspring health outcomes and offers a potential interventional strategy for preventing food allergies [137, 146]. Vitamin D receptors are found on T cells, B cells, and dendritic cells, and vitamin D has been posited to protect against the development of food allergy [147]. For example, a population‐based study of over 5000 infants found that vitamin D insufficiency was associated with an elevated risk of challenge‐proven peanut and egg allergy at 1 year of age [148]. However, conflicting data exist: a recent Japanese birth cohort study involving 82,592 mother–offspring pairs found that elevated maternal vitamin D consumption increased the odds of a child developing a self‐reported food allergy at 1 year of age [149]. In a Chinese population study involving over 20,000 questionnaires, maternal vitamin D consumption was negatively associated with self‐reported food allergy, whereas childhood vitamin D consumption was positively associated [110]. Polyunsaturated fatty acids (PUFAs) have also been proposed to mitigate allergic disease, as they are involved in immune cell regulation [150]. However, recent studies investigating maternal intake of these compounds have reported increased prevalence of self‐reported food allergy and atopic dermatitis in children aged 7–9 years in a Polish birth cohort [151], with no benefit for self‐reported food allergies in offspring in a Japanese birth cohort [152]. In the same Japanese cohort, a decrease in food allergy was observed among children whose mothers consumed higher amounts of isoflavones, suggesting that consuming isoflavone‐rich foods may reduce the likelihood of food allergy during infancy [153]. Because of its effects on the microbiome and immune regulation [154], dietary fiber is another impactful factor in the development of food allergies. While mouse studies have shown that a high‐fiber diet protects against food allergy by increasing short‐chain fatty acids production [155], compelling evidence that dietary fiber protects against food allergy in humans remains lacking.

Heavy metals, such as lead, cesium, cadmium, cobalt, and arsenic, are readily found in the food supply and can have negative health outcomes, especially in pregnant women and infants. Using data from NHANES, exposure to lead and cadmium was associated with increased total IgE quantities in adults, and lead exposure was associated with food sensitization [156]. Likewise, gestational urinary cadmium was found to increase the risk of physician‐diagnosed food allergy in children [157]. Surprisingly, exposure to certain heavy metals (e.g., cobalt, cesium, tin) during pregnancy was found to be inversely associated with allergic diseases, particularly in boys [158]. This conflicting evidence demonstrates that further studies are needed to confirm the risk of food allergy associated with heavy metals and better understand the underlying mechanisms.

Overall, evidence linking UPF and dietary additives to food allergy risk is mechanistically compelling but remains largely preclinical, and human epidemiological data are inconsistent. Given the growing public concern about the safety and health effects of food processing and additives, larger cohort studies are needed to determine whether these dietary factors modify the risk of food allergy.

7. Conclusion

Data from recent studies continue to add to the growing body of evidence that multiple environmental exposures during early life can modify the risk of food allergy (Table 1 and Figure 3). Environmental exposure to food allergens, particularly peanut, is increasingly recognized as a risk factor for allergic sensitization through the skin and possibly the respiratory tract. Microbial exposures in early life play an important role in shaping immune development by stimulating innate immunity and shaping the gut microbiome. Studies also suggest that co‐exposures to microbe‐derived adjuvants, such as endotoxin, can further modify food allergy risk. Exposure to air pollutants, including PM and NO₂, has been associated with food sensitization and allergy in birth cohort studies. There is growing concern that exposure to synthetic chemicals and detergents could contribute to food sensitization, but more well‐designed prospective cohort studies are needed. Food additives commonly found in ultra‐processed foods, including emulsifiers and preservatives, have been shown to disrupt gut barrier integrity; however, their association with food allergy risk remains unclear and warrants further investigation. Despite these findings, significant gaps remain in our understanding of the immune mechanisms by which environmental exposures promote food allergies, as well as the gene–environment interactions that influence disease risk. Longitudinal cohort studies that employ comprehensive exposome assessments are needed to address these knowledge gaps directly. Future studies should also test specific mechanistically grounded hypotheses, such as whether inhaled or cutaneous exposure to food allergens combined with particulate matter pollution increases peanut sensitization risk in infants with atopic dermatitis, whether house detergent residues modify epithelial barrier biomarkers and food sensitization in infancy, and whether reducing dietary consumption of AGEs or emulsifiers lowers food allergy risk. Addressing these hypotheses will help identify the key environmental drivers of food allergy and inform evidence‐based prevention strategies for patients and families (Box 2).

TABLE 1.

Recent studies of environmental exposures as risk factors for food allergy development.

Author/year	Exposure	Study design	Study population	Key findings
Lack et al., 2024	Environmental food	Observational	Younger siblings of LEAP participants	Younger siblings of LEAP participants who consumed peanuts had a higher rate of sensitization than siblings of peanut avoiders, suggesting that environmental exposure to peanuts was a risk factor.
Oliver et al., 2026	Environmental food	Environmental sampling	Homes in UK and US	Food allergens are airborne in residential environments, suggesting inhalation is a plausible route of exposure.
Jackson et al., 2025	Microbial	Birth cohort	Old Order Mennonite infants vs. urban controls	Farm exposure during infancy was associated with elevated IgG4 and mucosal IgA levels and lower egg allergy incidence.
Shibata et al., 2025	Microbial	Prospective birth cohort	Japanese infants	Bifidobacterium‐dominant neonatal gut microbiome was associated with a lower risk of food sensitization and allergy.
Gao et al., 2023	Microbial	Birth cohort	Australian infants	Gut microbiota maturation mediated the protective effect of older siblings on food allergy.
Stickley et al., 2025	Microbial	Birth cohort (CHILD)	Canadian infants	Specific microbes associated with decreased food sensitization in a genome‐ and exposure‐specific manner, establishing the role of gene‐by‐environment interactions in allergic sensitization.
Lopez et al., 2024	Air pollution	Birth cohort (HealthNuts)	Australian children	Elevated NO2 and PM2.5 exposure at 1 year of age was associated with persistent challenge‐proven peanut allergy through 10 years of age.
Immormino et al., 2024	Air pollution	Mouse model	Murine peanut allergy model	Airway co‐exposure to PM and peanut induced peanut allergy in mouse models, providing mechanistic insight into how air pollution drives food sensitization.
Lu et al., 2025	Air pollution	Retrospective cohort	Chinese preschoolers	NO2 exposure in the first trimester was associated with food allergy; PM10 and ozone were identified as postnatal risk factors.
Ghozal et al., 2025	Chemical	Prospective birth cohort (EDEN)	French mother–child pairs	Early‐life dietary exposure to chemical mixtures is associated with increased risk of an atopic multimorbidity cluster (including food allergy).
Ogulur et al., 2023	Chemical	In vitro/ex vivo	Human gut epithelial cells	A dishwasher rinse aid at a 1:10,000 dilution disrupted gut epithelial barrier integrity, suggesting household detergent residues impair epithelial barrier function.
Zhang et al., 2025	Chemical	Cross‐sectional population study	Chinese children	Phthalate exposure is associated with higher total IgE and increased food sensitization risk.
Paparo et al., 2024	Dietary	Cross‐sectional + in vitro	Food‐allergic children vs. controls	Food‐allergic children had higher dietary AGE intake; AGEs increased transepithelial allergen passage and stimulated Th2 cytokines.
Zhang et al., 2025	Dietary	Cross‐sectional survey, in vitro/ex vivo models	NHANES data, mouse food allergy model, human PBMCs	AGE‐rich diet was associated with self‐reported food allergy; oral AGEs induced intestinal barrier dysfunction and food allergy in mice, and stimulated Th2 responses by human PBMCs.
Lamas et al., 2024	Dietary	Mouse model	Murine oral tolerance model	Chronic oral exposure to the food additive silicon dioxide prevented the induction of oral tolerance.
Kampouri et al., 2023	Dietary	Prospective birth cohort	Swedish mother–infant pairs	Gestational cadmium exposure is associated with increased risk of food allergy or eczema at 1 year.
Islam et al., 2026	Multiple	Meta‐analysis	190 studies involving 2.8 million participants	Identified antibiotic exposure, delayed allergen introduction, and birth‐related variables as risk factors for food allergies.

FIGURE 3.

The external exposome impacts food allergy risk. Several environmental exposures, including environmental food allergens, microbes, air pollutants, synthetic chemicals, and dietary additives, can significantly affect the developing immune system during early life. The combination of these exposures, along with genetic susceptibility factors, plays a critical role in determining the risk of food allergy. Created with BioRender.com.

BOX 2. Future research perspectives.

• Conduct prospective, longitudinal cohort studies that integrate comprehensive exposomic‐based approaches with clinically diagnosed food allergy outcomes to establish causal relationships between specific environmental exposures and food allergy development.

• Improve the standardization of environmental assessment tools to enhance comparisons across cohort studies.

• Investigate gene‐by‐environment interactions that modify individual susceptibility to environmental risk factors for food allergies.

• Develop biomarkers that better define the site of allergic priming to elucidate the contribution of cutaneous and airway exposures in food sensitization.

• Expand research beyond peanut to determine if other environmental food exposures (e.g., milk, egg, tree nuts, sesame) increase food allergy risk.

• Examine whether the indoor microbiome modifies food allergy risk by acting as a source of microbial adjuvants or shaping the host microbiome.

• Elucidate the mechanisms by which synthetic chemicals can damage epithelial barriers and promote Th2‐skewed immune responses.

• Perform well‐powered prospective studies to define how ultra‐processed foods and dietary additives affect food allergy risk.

• Assess whether modifiable environmental exposures (e.g., farm‐associated microbes, microbe‐derived adjuvants, dietary fiber) can be leveraged as preventative strategies for food allergies.

Author Contributions

Johanna M. Smeekens: investigation, writing – review and editing. Helen A. Brough: investigation, writing – review and editing. Kirsi M. Järvinen: investigation, writing – review and editing. Sophie Troyer: investigation, writing – review and editing. Michael D. Kulis: investigation, writing – review and editing. Timothy P. Moran: conceptualization, investigation, supervision, writing – original draft preparation, writing – review and editing.

Funding

This work was supported by funding from the National Institute of Health (R01‐ES032544 to T.P.M.).

Conflicts of Interest

T.P.M. receives research funding from the National Institutes of Health (NIH) and the American Heart Association, and speaker honoraria from Food Allergy Research and Education (FARE). H.A.B. discloses research grants from the NIH; research support from Primus; speaker honoraria from IH; research support from Primus; speaker honoraria from Thermo Fisher Scientific, DBV Technologies, Viatris, Stallergenes; and advisory board services for NICE, Viatris, Parexel, and CoFAR. K.M.J. reports funding from the NIH, DBV Technologies, and Siolta; and consulting for Danone and Mill Care Co.

References That Are of Particular Interest

Y. Gao, J. Stokholm, M. O'Hely, et al., “Gut Microbiota Maturity Mediates the Protective Effect of Siblings on Food Allergy,” Journal of Allergy and Clinical Immunology 152, no. 3 (2023): 667–675.

• This Australian birth cohort study found that having older siblings accelerates the maturation of the infant gut microbiome, which is associated with protection against food allergy.

D. J. Lopez, C. J. Lodge, D. S. Bui, et al., “Air Pollution Is Associated With Persistent Peanut Allergy in the First 10 Years,” Journal of Allergy and Clinical Immunology 154, no. 6 (2024): 1489–1499.e9.

• This analysis of the Australian HealthNuts birth cohort study found that elevated exposures to NO₂ and PM_2.5 at Age 1 were associated with persistent challenge‐proven peanut allergy through Age 10.

R. M. Immormino, J. M. Smeekens, P. I. Mathai, et al., “Different Airborne Particulates Trigger Distinct Immune Pathways Leading to Peanut Allergy in a Mouse Model,” Allergy 79, no. 2 (2024): 432–444.

• This preclinical study found that co‐exposure to peanut and PM induced peanut allergy in a mouse model, providing mechanistic insights into how air pollutant exposure may increase food allergy risk.

N. Islam, A. W. L. Chu, F. Sheriff, et al., “Risk Factors for the Development of Food Allergy in Infants and Children: A Systematic Review and Meta‐Analysis,” JAMA Pediatrics 180 (2026): 480–499.

• This meta‐analysis of 190 studies involving 2.8 million participants found several environmental factors associated with increased risk of food allergy, including antibiotic exposure, delayed allergen introduction, and being a firstborn child.

C. M. Jackson, E. Ponko, N. M. Vance, et al., “Farm Exposure in Infancy Is Associated With Elevated Systemic IgG(4), Mucosal IgA Responses, and Lower Incidence of Food Allergy,” Science Translational Medicine 17, no. 828 (2025): eads1892.

• This birth cohort study found that Old Order Mennonite infants had lower rates of food allergies and elevated levels of systemic IgG4 and mucosal IgA compared with urban/suburban children, providing evidence that exposure to farming during infancy can alter immune responses and may protect against food allergies.

I. Ogulur, Y. Pat, T. Aydin, et al., “Gut Epithelial Barrier Damage Caused by Dishwasher Detergents and Rinse Aids,” Journal of Allergy and Clinical Immunology 151, no. 2 (2023): 469–484.

• This preclinical study found that a dishwasher rinse aid at dilutions as low as 1:10,000 could disrupt human gut epithelial cells, suggesting that household detergent residues can impair epithelial barrier integrity, thereby increasing the risk of allergic inflammation.

M. A. Oliver, R. T. Meredith, M. D. Bermingham, et al., “A Novel Ambient Air Sampler for Detection of Allergens and Endotoxin,” Journal of Allergy and Clinical Immunology: Global 5, no. 3 (2026): 100677.

• This environmental sampling study showed that airborne food allergens are detectable in homes, providing evidence that inhalation of food allergens is a plausible route of exposure.

L. Paparo, S. Coppola, R. Nocerino, et al., “How Dietary Advanced Glycation End Products Could Facilitate the Occurrence of Food Allergy,” Journal of Allergy and Clinical Immunology 153, no. 3 (2024): 742–758.

• This study, which included cross‐sectional surveys and in vitro models, showed that food‐allergic children had increased consumption of dietary AGEs, and that AGEs impair epithelial barrier integrity and stimulate Th2 cytokine production by peripheral blood immune cells.

R. Shibata, Y. Nakanishi, W. Suda, et al., “Neonatal Gut Microbiota and Risk of Developing Food Sensitization and Allergy,” Journal of Allergy and Clinical Immunology 155, no. 3 (2025): 932–946.

• This prospective birth cohort of Japanese infants found that a Bifidobacterium‐dominant neonatal gut microbiome was associated with lower risk for food sensitization and allergy.

Q. Zhang, G. Yu, Y. Jiang, et al., “Dietary Advanced Glycation End‐Products Promote Food Allergy by Disrupting Intestinal Barrier and Enhancing Th2 Immunity,” Nature Communications 16, no. 1 (2025): 4960.

• This study showed that an AGE‐rich diet was associated with self‐reported food allergy in the NHANES dataset, and that AGES induced intestinal barrier dysfunction and promoted Th2 cytokine production by immune cells.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during this study.