Edible Insects and Allergy Risks: Implications for Children and the Elderly

Abstract

Population growth and the depletion of natural resources have driven the incorporation of edible insects into the human food matrix. Despite their high nutritional value and the environmental benefits of insect farming compared to conventional protein sources, their consumption poses potential risks, including food allergies. Sensitization to insect allergens can occur through various exposure routes, with cross-reactions involving other foods and environmental allergens being well-documented. Vulnerable groups such as children and the elderly may have increased susceptibility not only because of genetic predisposition but also because of age-related physiological factors. This review explores the emerging risks of edible insect consumption, with a focus on children and the elderly. Age-related alterations in the gut microbiota, digestion, immune function, and overall physiology can facilitate the absorption of intact allergenic proteins and impair immune responses. Furthermore, the allergenic potential of insect proteins and their associated microbiota remains poorly characterized. Limited research exists on the effects of processing methods on these proteins. Consequently, incorporating edible insects into food products could present an additional allergenic risk, particularly for these vulnerable populations. Understanding these risks is essential for ensuring the safety and acceptance of edible insects as sustainable food ingredients.

1. Introduction

Population growth estimates for the coming years and anthropogenic climate change issues are the main drivers of the search for alternative food sources to traditional models. According to the Food and Agriculture Organization (FAO), the expected global population growth is around 9 billion people by 2050. This scenario demands that food production grows almost double [1]. However, limited natural resources necessitate the pursuit of more sustainable alternatives.

Edible insects emerge as a promising source of nutrients due to their lower environmental impact compared to livestock and poultry production [2]. While the nutritional composition varies significantly based on factors such as species, life stage, and diet, edible insects are generally rich in protein (7 to 91% of dry matter) [3] and essential amino acids [4]. They are low in sodium and typically contain 30% fat, and are rich in unsaturated fatty acids, such as linoleic and linolenic acids [3]. Carbohydrates constitute approximately 10%, and chitin, a fiber source, exhibits prebiotic and bioactive properties [3,4]. Furthermore, insects can be a valuable source of minerals, such as phosphorus, manganese, copper, selenium, zinc, iron, and calcium [4].

Edible insects are a rich source of B vitamins, including thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), and cobalamin (B12). Furthermore, certain insects may contain carotenoids, which act as precursors to vitamin A and, although less commonly, vitamin D [3].

Despite their nutritional benefits, significant knowledge gaps remain regarding the potential of edible insects to trigger allergic reactions in susceptible individuals. Accurately identifying these individuals poses a major challenge. Potential allergic responses include eczema, rhinitis, conjunctivitis, angioedema, and bronchial asthma. Furthermore, documented cases of allergic reactions following the consumption of edible insects include anaphylactic shock [5].

Insects are recognized as significant sources of allergens for humans. Allergic reactions can be triggered by bites, stings, inhalation, and ingestion [6]. While allergic responses to insect venom, contact, and inhalation are well documented, the allergenic potential of edible insects consumed as food remains relatively unexplored.

Allergy is a systemic immune response primarily affecting organs interfacing with the external environment, such as the skin, respiratory system, and gastrointestinal tract [7]. Food allergies can arise through IgE-mediated or non-IgE-mediated mechanisms [8]. In this context, insects represent a significant source of sensitization and allergenicity for humans. Exposure to insect particles through inhalation, as well as bites, stings, or ingestion of edible insects, can trigger allergic reactions. The sensitization profiles and severity of allergic responses to these allergens vary significantly among individuals and across populations [6].

According to European food legislation and the Food and Drug Administration (FDA) guidelines, each application involving edible insects must be supported by a comprehensive scientific evaluation demonstrating their safety [9,10]. However, assessing the potential risks and providing evidence that novel foods are unlikely to trigger allergic reactions remain significant challenges. Establishing sufficient evidence of the allergenicity of each edible insect necessitates reliable diagnostic approaches, standardized testing, and strict diagnostic criteria. This includes detailed clinical histories of reactive individuals and labor-intensive experimental methods. Currently, no widely adopted methodologies are available for diagnosing or investigating food allergies related to insect consumption [11].

The absence of specific regulations for edible insects has created uncertainty regarding their safety as a food source. This uncertainty primarily stems from the difficulty in accurately predicting whether edible insects pose an allergenic risk.

This review aims to investigate the emerging risks associated with the consumption of edible insects, focusing on the potential for allergic reactions. Therefore, an overview of food allergies and allergic diseases is provided herein, including their development, characteristics, and the influence of the food matrix and processing on allergen properties. Furthermore, this review specifically explores the potential vulnerability of certain populations, such as children and the elderly, to adverse reactions from edible insect consumption.

2. Emerging Allergy Risks from Edible Insect Consumption

2.1. Food Allergies: An Overview of Allergic Diseases and Food Allergy Development

Food sensitivities, allergies, and intolerances represent individualized adverse reactions to specific foods [12]. Notably, many individuals exhibit sensitization to multiple foods without necessarily experiencing clinical reactions or true allergic responses to all of them [13]. It is crucial to distinguish between food allergies, which are immune-mediated processes, and food intolerances, which are non-immune-mediated reactions [14]. The primary foods (and their products or derivatives) commonly associated with food intolerances include cereals containing gluten (e.g., wheat, rye, barley, oats, spelt, or their hybridized strains), crustaceans, eggs, fish, peanuts, soybeans, milk, tree nuts, and sulfites [15].

Food allergy is defined as an adverse health effect resulting from a specific immune-mediated response that occurs reproducibly upon oral exposure to a particular food. This response can either involve or not involve food-specific immunoglobulin E (IgE) antibodies [15]. In such cases, proteins have been observed to elicit abnormal immune responses [12]. In the context of food allergies, the triggering of symptoms may occur with lower doses of the allergen than those required for the development of sensitivities and intolerances [12].

Symptoms of IgE-mediated allergies can range from mild itching to life-threatening anaphylactic reactions [16]. Immunoglobulin E (IgE)-mediated reactions are characterized by their rapid temporal profile, culminating in a variety of clinical manifestations. These include, but are not limited to, pruritus, urticaria, erythema, dyspnea, and systemic anaphylaxis, with consequent involvement of multiple physiological systems, including the cutaneous, ocular, gastrointestinal, respiratory, and cardiovascular systems [16]. In the context of food allergy, the most commonly observed IgE-mediated reactions manifest as localized phenomena such as acute urticaria and angioedema, oral allergy syndrome, and immediate gastrointestinal hypersensitivity, alongside the potentially life-threatening systemic response of food-induced anaphylaxis. In addition, specific IgE-mediated food allergy syndromes, such as alpha-gal syndrome and food- and exercise-induced anaphylaxis, are recognized as distinct clinical presentations of IgE-mediated food allergy [17].

Initial exposure to a food allergen has been shown to lead to sensitization in some individuals, yet others demonstrate an absence of a clinical response to allergen ingestion following sensitization [17]. The process of eliciting a response necessitates the binding of IgE antibodies to receptors located on the surface of mast cells and basophils. Subsequent exposure to the allergen results in the cross-linking of two or more IgE antibodies, thereby triggering their degranulation. This process leads to the release of physiologically active allergic mediators, including histamine, leukotrienes, and prostaglandins, which ultimately trigger an allergic reaction [12].

In contrast, chronic allergic inflammation is predominantly mediated by T cell-driven responses, rather than IgE-triggered mast cell activation, despite the eventual presence of allergen-specific IgE in affected individuals. The processes mainly occurring in the intestine are responsible for the syndromes of food protein-induced allergic proctocolitis, enterocolitis, and eosinophilic esophagitis [18].

Although food sensitization can occur through various routes, including ingestion, the innate immune system is activated against allergens at the site of exposure [19]. Genetic susceptibility to allergy, allergen characteristics (structural features, 2D and 3D epitopes, enzymatic activity, influence of post-translational modifications, particularly glycosylation, and physicochemical properties such as stability and resistance to proteolytic digestion) [13], the route of exposure (ingestion, skin contact, or inhalation), food matrix components (and their effects), and the composition of the microbiota have been shown to influence the development of food sensitization [13,20]. Classic exposure to food allergens occurs through ingestion. However, food allergy reactions in allergic individuals can be triggered by environmental exposure, such as when food proteins remain on surfaces or in the air [21].

Notably, allergic diseases, including food allergies, have increased dramatically in recent years, a phenomenon that cannot be solely explained by genetic predisposition [21].

The development of IgE-mediated allergies can often occur early in life, involving a combination of inherited genetic susceptibility and early environmental exposures [7]. The prevalence of food allergy is highest during the first five years of life, affecting approximately 6% of infants under the age of three [22]. Although most studies do not include clinical investigations, data suggest that the overall prevalence of IgE-mediated food allergy may be as high as 8% to 10% across all age groups in the United States [12].

Although the intestinal epithelium acts as a barrier that restricts the permeation of macromolecules through tight junctions, some allergenic proteins can cross the intestinal barrier intact [23,24]. The major food allergens that can promote allergy after crossing the gastrointestinal tract are typically water-soluble glycoproteins with a size range of 0 to 70 kD. These proteins are relatively stable to heat, acid, and proteases, both during food processing and digestion [25].

Factors that enhance the permeability of the small intestinal mucosa to proteins have been proposed as contributing to the onset of food allergies [26]. During early development, the immaturity of various components of the intestinal barrier and immune system compromises the efficiency of the infant’s mucosal barrier [22].

Individuals with a genetic predisposition to food sensitivity exhibit heightened susceptibility to food allergies. The etiology of food allergy arises from an abnormal state of immune tolerance, influenced by antigen exposure, gut dysbiosis, and their interactions. Gut dysbiosis may either precede the development of food allergy [27] or emerge as a consequence of allergic inflammation, as suggested by some murine model studies [21]. Certain groups of bacteria have been found to be differentially abundant in children with food allergies and in murine models, suggesting a role in their sensitization [27,28]. The gut microbiome undergoes significant changes throughout life, with the most rapid changes occurring early in life and during aging [20,28]. In this regard, the gut microbiota likely plays multiple complex roles in the initiation, regulation, and promotion of allergic sensitization [21].

2.2. Food Allergies and Insects: An Interconnected Perspective

Structural homology between allergens can result in the binding of cross-reactive IgE antibodies, termed cross-sensitization, which may or may not be symptomatic. In contrast, cross-reactivity refers to the induction of symptoms consistent with IgE-mediated food allergy [29,30], that is, the development of food allergy in individuals who have already been exposed and sensitized to structurally similar non-food allergens [18].

Edible insects have the potential to promote allergenicity through direct or cross-sensitization. Co-allergy to multiple foods can develop as a result of an atopic predisposition to develop IgE antibodies to many proteins in the diet or environment. In contrast, allergy to cross-reactive foods results from IgE binding to homologous proteins or epitopes that are conserved between related foods [31]. Allergic cross-reactivity often occurs as a symptom in the absence of prior exposure or after exposure to allergenic sources that are unlikely to sensitize.

Airborne insect particles have been identified as a significant cause of respiratory allergies, including allergic asthma and rhinitis. A wide range of symptoms have been reported in response to exposure to insects such as crickets, locusts, and larvae of the bee moth, as well as mealworms. Cockroach allergy is mainly associated with inhalant allergy [6]. However, a correlation has been demonstrated between sensitization to cockroaches and house dust mites and the risk of food allergy to shrimp [11]. The prevalence of sensitization to cockroaches exhibits notable variations across different regions, with higher rates typically observed in warmer climates [6].

Among the various components of insects, chitinases have been identified as a significant source of food allergens, with their origins being predominantly from plant sources, such as avocado, banana, papaya, tomato, chest fruit, kiwi fruits, green bean, wheat, rice, coffee green beans, raspberry berries, Indian jujube fruit, pomegranate, grape, and maize [32]. This syndrome has been observed to be associated with both plant and insect chitinases [32], underscoring the complexity and potential risks involved in the consumption of edible insects.

Various insects containing a number of allergens have been identified as potential triggers for cross-reactive allergies, including arginine kinase [33,34], tropomyosin [35,36], glyceralde-hyde-3-phosphate dehydrogenase [37], hexamerin 1B [34,37], sericin [38], hemocyanin [39,40], troponin C [41], sarcoplasmic calcium-binding protein, sarcoplasmic endoplasmic reticulum calcium ATPase, phospholipase, and other minor allergens [14]. A significant number of allergens involved in primary and cross-reactivity responses have been previously documented in the scientific literature, but only a few isoforms have been officially recognized [11]. Tropomyosin, glutathione S-transferase, and arginine kinase, which often result in IgE cross-reactivity between extracts from different insect (and other arthropod) species. However, the species-specific allergen components of most insect species other than cockroaches have not been well characterized [6].

The insects associated with these allergens include silkworm (Bombyx mori), mealworm (Tenebrio molitor), buffalo worm (Alphitobius laevigatus), locust (Locusta migratoria, Schistocerca americana), grasshopper (Locusta migratoria, Schistocerca americana, Poecilocerus pictus), cricket (Acheta domesticus, Gryllus bimaculatus, Gryllus sigillatus, Teleogryllus commodus), termite (Coptotermes formosanus), cockroach (Blattella germanica, Blattella americana), fruit fly (Drosophila melanogaster), and black soldier fly (Hermetia illucens) [11].

While defining the exact number of edible insects is challenging due to varying consumption patterns across regions, all insects reported as allergenic were also reported as edible in the first available compilation on the subject [42,43].

Studies on the cross-reactivity of crustaceans have demonstrated a high degree of sequence similarity with tropomyosin. Sequence identity ranges from 75 to 80% between shrimp, house dust mite, and American cockroach [14]. Tropomyosin belongs to a family of highly conserved proteins with multiple isoforms found in both muscle and non-muscle cells of all species of vertebrates and invertebrates. Tropomyosin has been hypothesized as a cross-reactive allergen, responsible for the immunological relationship between crustaceans, cockroaches, and house dust mites [35]. This phenomenon can be attributed to the conservation of IgE epitopes between crustacean and insect tropomyosin sequences, underscoring the potential for cross-reactivity [40].

Moreover, research has indicated that arginine kinase, a constituent of the Bombyx mori silkworm, has been identified as the primary allergen exhibiting cross-reactivity with cockroach allergen [33].

Inhalation is a recognized route of exposure and sensitization that can lead to food allergy. As many allergens from house dust mites and cockroaches share significant homology in IgE cross-reactivity with shellfish allergens [6], these allergens may also be capable of eliciting responses from edible insects.

In addition to the allergic reactions caused by cross-reactivity in shellfish-allergic individuals, insect proteins also have the potential to sensitize individuals themselves. Between 1980 and 2007, 63 cases of anaphylaxis due to the consumption of insects such as locusts (27), grasshoppers (27), silkworm pupae (5), cicada pupae (1), bee pupae (1), bee larvae (1), and Claris bilineata (1) were reported [44].

It is likely that this small number of reports underestimates the true extent of food insect allergies. Therefore, limited information is currently available on sensitization and food allergy reactions due to the consumption of edible insects. Most studies have shown classic symptoms of allergy such as anaphylactic reactions, urticaria, pruritus, itching, edema, and respiratory distress requiring medical intervention. However, there is a lack of information on reactions that are less expressive or unrecognized as allergic symptoms. Comprehensive studies of areas where insects are intentionally consumed could help to better understand the relationship between edible insects and direct sensitization or cross-reactivity in the development of food allergy reactions.

2.3. Food Allergen Characteristics: Implications for Allergenicity

In addition to the major foods or food groups recognized by FAO, over 160 other foods have been documented to cause IgE-mediated food allergy. Since food allergens are proteins, any protein-containing food has the potential to induce allergic sensitization, at least in some cases [12].

The introduction of insect-based food ingredients presents two distinct allergenicity risks. The first is the potential for cross-reactivity between ingested insects and taxonomically related species to which an individual has an existing allergy. The second risk arises from the ability of the insect ingredients themselves to sensitize individuals and cause food allergies [14].

Certain allergen characteristics, such as solubility, stability, molecular properties, and molecular size, are crucial for reaching organ-specific immune induction sites and promoting allergies. The classic type 1 food allergens (found in cow’s milk, egg white, peanut, and soybean), capable of inducing IgE sensitization across the gastrointestinal mucosa, are heat- and acid-stable, water-soluble glycoproteins ranging in size from 10 to 70 kDa. Food allergens can be broadly classified as heat-stable or heat-labile. Heat-stable food allergens possess molecular properties that engender conformational stability. These properties comprise disulfide bonds, protein glycation, and the capacity to bind lipids and protect food allergens from degradation by heat, acid, and proteases, thereby facilitating better absorption of intact protein in the gastrointestinal tract [29].

The route of allergen access by the human immune system dictates specific molecular requirements for allergen uptake. For dermal absorption, the allergen must be able to traverse the epidermal barrier, which exhibits both hydrophobic and hydrophilic properties that modulate skin permeability. Thus, allergens penetrating the outer barrier of intact skin typically possess hydrophobic properties or are bound to a lipophilic carrier. Inhaled allergens do not require specific stability to low pH or enzymes but must exhibit sufficient solubility in the aqueous environment and the appropriate particle size to enter and escape the mucus-binding properties of the respiratory tract [45]. Allergens sensitizing via the gastrointestinal tract require high protein stability to withstand proteolytic and hydrolytic degradation. Following thermal processing of food, major allergens will only elicit an allergic response via the oral route if they are heat-resistant [46].

To be considered stable, a food allergen must maintain its native protein structure, defined by its three-dimensional configuration, even in the presence of external factors such as chemical, physical, or protease attacks over time [45]. Notwithstanding, specific regions within the allergen protein, known as epitopes, are recognized by antibodies and determine its allergenic character [47].

Pan-allergens, such as tropomysion, are food allergens that can trigger reactions to crustaceans as well as to mites and insects [6,48]. This effect has also been observed when cross-reactivity occurs between patients with inhalant and food allergies [6,49]. Tropomyosin and arginine kinase have been identified as cross-reactive proteins. Consequently, individuals allergic to crustaceans and house dust mites may also exhibit allergies to foods containing proteins from mealworm larvae [48,50].

Cross-reactivity between different allergens occurs due to shared or identical IgE-binding epitopes. These shared epitopes may be the origin of sensitization and the development of allergic symptoms to allergens found in closely or distantly related species [35]. Consequently, even following a conformational modification of the allergen protein, if epitopes from the core of the molecule become exposed, the potential for allergy not only persists but may be amplified [51]. This underscores the significance of understanding the matrix of food allergens, as well as the processing of food.

3. The Impact of Processing on Edible Insect Allergenicity

3.1. The Influence of the Food Matrix on Allergenicity

Food is a complex matrix where food allergens are primarily released during processing, oral handling, and digestion. Furthermore, the components of the food matrix significantly influence their allergenic potential [25].

The impact of the food matrix on gastrointestinal degradation and the uptake of food allergens can have both negative and positive consequences for susceptible individuals [24]. The composition of the food also interferes with physiological processes that impact the expression of the allergen’s allergenicity. Following ingestion and throughout the gastrointestinal tract, several biochemical processes favor the proteolysis of allergens. The degree of proteolysis correlates with allergenicity, with a reduction in allergenicity observed as proteolysis increases [45].

However, depending on the matrix and the configuration of the allergen protein within this matrix, proteolysis may exert a detrimental effect on allergenicity. The sensitization to an allergen ingested is influenced not only by the stability of the allergen in the gastrointestinal tract, but also by the presence, abundance, and availability of epitopes with immunostimulatory capacity. Consequently, proteolysis has the capacity to modify the protein structure, disrupting linear epitopes, but may be exposing or reconfiguring conformational epitopes that were previously inaccessible within the protein interior [47].

High protein and carbohydrate content in foods has been shown to increase their stability against simulated gastrointestinal degradation [24,25]. This phenomenon can be attributed to the inhibitory effect of polysaccharides on pepsin activity [24]. In carbohydrate-rich foods, allergens may be easily masked by the matrix effect, limiting the exposure of allergenic epitopes [25]. Consequently, protein and carbohydrates play a significant role in protecting food allergens [24]. Furthermore, foods with high carbohydrate and lipid content have been shown to slow down digestion, resulting in the prolonged release and absorption of allergens within the gastrointestinal tract [23,24]. Lipids can enhance the ability of allergens to resist digestion and promote their passage across the epithelial barrier as intact molecules, while also potentially modulating the immune response to allergens [25]. Moreover, protein interactions with other food matrix components, including other proteins, lipids, and sugars, in processed foods, generally diminish protein availability for interaction with the immune system [51].

Minerals and vitamins, while minor components of the food matrix, can influence epitope structure by forming ligands with allergens, either masking or unveiling epitopes and modulating their allergenicity. Furthermore, minerals and vitamins are known to participate in the immune response, exerting a tangible influence on the manifestation of food allergies [25].

The nutritional composition of edible insects varies considerably between species. Based on dry matter, the protein content of various edible insects ranges from 5 to 77%, with average values between 35 and 61% [2], and the fat content ranges from 13 to 33%. Chitin, a polysaccharide of N-acetyl-D-glucosamine, is the main component of the exoskeleton [14]; its content depends on the insect species and developmental stage [49].

The components of the food matrix can impact the allergenic properties of food insects during both digestion and processing. Chitin has been identified as a molecular structure with potential immunomodulatory effects. Evidence suggests that chitin may promote the production of allergen-specific IgE antibodies, which are pivotal in the pathogenesis of immediate hypersensitivity reactions [49].

Food allergens often remain active after heat, dry, or wet processing. In many cases, processing, similar to proteolysis, promotes the exposure of epitopes, potentially increasing the risk of allergic reactions [25,47].

Furthermore, reactions between food matrix components can alter the reactivity of the food allergen. This scenario is further complicated by the lack of specific data on food insect matrices, including the effects of food processing on the allergenicity of these products.

3.2. The Effect of Processing on Food Allergenicity

After collection, farmed insects are killed through processes such as freeze-drying, sun-drying, or boiling. They can then be consumed whole, processed by grinding or pasteurization, or further processed to obtain ingredients like protein, fat, or chitin extracts for the fortification of food and feed products. The isolation and extraction of insect protein is desirable to increase the protein content of a food product or enhance its acceptability to wary consumers [1]. Insect protein can also serve as a protein substrate for obtaining bioactive peptides with applications in the food, nutraceutical, and pharmaceutical industries [52].

However, food supplementation requires extensive knowledge of the extracted proteins’ properties, including amino acid profile, thermal stability, solubility, gelling, foaming, and emulsifying ability [1].

Food processing exerts diverse effects on different food allergens, even within the same food matrix. These processes alter the physicochemical properties of the food system, with implications for food allergy. Proteins possess a complex structural organization that maintains their stability [53]. Any disruption of this intrinsic organization will affect the protein’s allergenicity.

Interactions with other proteins, fats, and carbohydrates within the food matrix are complex and poorly understood, hindering the elucidation of food protein interactions with gut-associated lymphoid tissue and their consequences [51].

Thermal processing is categorized into dry heating (e.g., roasting, oil frying, baking, infrared and ohmic heating) and wet heating (e.g., boiling, autoclaving, extrusion, and cooking) [54]. The impact of temperature on allergenic proteins is influenced by various factors, including the specific allergen type, processing conditions, and the composition of the food matrix. Studies on the physiological response of organisms to allergens indicate that thermal processing can either reduce or increase allergenicity. For instance, peanuts and shrimp have been shown to exhibit heightened allergenicity at elevated temperatures due to the Maillard reaction—a chemical process involving the interaction of free amino acids with aldehyde or ketone groups in sugars [51].

The effect of thermal processing on allergens is contingent on the presence of water. Wet processing, which encompasses a range of techniques such as boiling, extrusion, and cooking, is the most prevalent processing method [53]. When matrices contain heat-denatured proteins, hydrophobic groups of the proteins become exposed to the surrounding water, favoring aggregation [55]. Heating unfolds tertiary and secondary structures, exposing the inner molecule, leading to denaturation. Aggregation results from internal modifications of the protein under heat due to intermolecular changes and chemical reactions. Heating destroys most conformational epitopes by unfolding native proteins, but leaves linear epitopes intact, which are the primary contributors to allergies due to their resistance in the gut [55].

Conversely, non-thermal processing encompasses a wide range of techniques used to process food without heating. Non-thermal processing includes various techniques such as enzymatic digestion, high hydrostatic pressure, ultrafiltration, fermentation, gamma irradiation, pulsed ultraviolet light, ultrasound, etc., which produce different results depending on the process conditions, the food matrix, and the allergen protein [53,56].

However, current food processing methods, including both conventional thermal processing and novel technologies, have proven ineffective in completely eliminating allergenicity. Indeed, even microbial fermentation and enzymatic or acid hydrolysis, while reducing the effects of allergenic proteins in some cases, do not completely eliminate their allergenic effects [57]. This phenomenon can be attributed to the presence of linear epitopes within the allergens, which possess immunostimulating properties. These epitopes, located within the proteins, are more protected from the effects of these treatments and from proteolysis during passage through the digestive tract [45].

Despite the majority of studies conducted thus far focusing on allergens found in traditional food matrices, some insect allergens have been described. In a systematic review, the most common insect species causing allergic reactions were silkworm pupae, grasshoppers, and locusts [58]. Two allergens of silkworm pupae have been identified as possible cross-reactive allergens of house dust mites: the chitinase precursor and paramyosin [59]. Chitinase is an essential enzyme in the gastrointestinal tract of cockroaches, responsible for digesting chitin by hydrolyzing the N-acetyl-D-glucosamine 1,4-β bonds of chitin polymers. Chitinase allergens have also been found in house dust mite allergens [47].

The allergenic proteins found in Bombay locust showed varying responses to deep-frying. Thermal processing caused a decrease in the allergenicity of arginine kinase, enolase, and HEX, but increased the effect of glyceroldehyde-3-phosphate dehydrogenase and pyruvate kinase [34]. In addition, Bombay locust food allergens exhibited cross-reactivity with shrimp allergens [34]. Silkworm pupae, a nutritious food regularly consumed in China, India, and other countries with developed sericulture, can retain their allergenicity, likely due to chitinase and paramyosin, even when eaten fried or boiled [32,44,59].

Furthermore, although heat treatment has been demonstrated to alter the solubility of yellow mealworm proteins [60], it does not appear to reduce the allergenicity of mealworm (yellow mealworms (Tenebrio molitor L.), super mealworms (Zophobas atratus Fab.), and lesser mealworms. (Alphitobius diaperinus Panzer) proteins (tropomyosin and arginine kinase), nor the IgE-binding capacity nor IgE cross-linking functionality, though it modifies the protein solubility [60,61].

It is well-established that heat treatments can increase the allergenicity of certain foods. For instance, high temperatures can enhance the allergenicity of peanut and shrimp proteins through a process known as glycation, which involves the reaction between free amino acids and aldehyde or ketone groups of sugars. Peanut proteins, specifically Ara h 1, Ara h 2, and Ara h 6, have been observed to demonstrate heat resistance, and their allergenicity has been shown to be amplified when subjected to dry heat [51,62,63]. Processes such as dry roasting have been found to result in glycation and the formation of Ara h 2 aggregates, which have been demonstrated to enhance allergenicity [51]. However, limited studies have examined whether this same behavior will be observed among proteins from edible insects.

A complex and as yet poorly understood microbiota is present in edible insects, found in various parts of the body. Controlled farming conditions and thermal treatment can guarantee microbiological safety, but they may not eliminate the proteins already produced by gut microbiota. These proteins will therefore be coextracted during the production of insect protein concentrate, and their content may be particularly relevant for insects with a high proportion of gut and gut content in the total mass [49]. There is currently not enough evidence to determine whether insect protein concentrates pose a health risk. This is due to the fact that their gut proteins are produced by an equally poorly understood microbiota. Furthermore, research is required to ascertain how insect proteins are affected by processing, considering their possible interactions with the matrix. This understanding is essential for the development of food allergies due to the consumption of edible insects and their derivatives.

4. Edible Insects and Allergies: A Focus on Vulnerable Individuals

All novel food protein sources possess the potential to elicit allergic reactions. However, the emergence of clinically significant food allergies typically requires multiple exposures, widespread consumption, and an extended period of time [14]. Importantly, the identification of a protein as an allergen does not inherently imply a significant risk of food allergy unless this allergen source is commonly consumed in substantial quantities [64].

The utilization of edible insects as a protein source and as an ingredient in various industrial products has the potential to increase allergen exposure. This heightened risk can be attributed to the fact that the processing of insect protein can result in the concentration of allergens. Additionally, the incorporation of insect protein as an ingredient in processed products may inadvertently lead to increased consumption.

The industry has demonstrated a growing interest in producing insect-derived products, such as protein concentrates. This increased interest can be attributed to the acknowledgment that a considerable number of consumers have substantial reservations regarding the aesthetic qualities and even the gustatory experience of whole insects [65,66].

Furthermore, research indicates that edible insects exhibit structural similarities with known allergens found in more widely consumed arthropods [14]. This finding prompts concerns regarding the potential for cross-reactivity and allergic reactions in individuals with pre-existing allergies.

The majority of countries have not yet established precise and insect-specific legislation, standards, labeling, and other regulatory instruments to govern the production and commercialization of insects in both food and feed supply chains [15]. The European Community (EU) established the Regulation (EU) 2015/2283, which describes the process to evaluate edible insects as a novel food. Since then, the EU has approved the use of only eight insect species as feed materials, namely: Tenebrio molitor, Alphitobius diaperinus, Acheta domesticus, Gryllodes sigillatus, Gryllus assimilis, Bombyx mori, Hermetia illucens, and Musca domestica [66].

The European Food Safety Authority (EFSA) has conducted a series of evaluations on the safety of a limited number of products derived from insect species for human consumption. These evaluations have led to the approval of larvae from four insect species for marketing: the yellow mealworm (Tenebrio molitor), the migratory locust (Locusta migratoria), the house cricket (Acheta domesticus), and the lesser mealworm (Alphitobius diaperinus). The evaluation also encompassed the banded cricket (Gryllodes sigillatus), the black soldier fly (Hermetia illucens), and the male pupa of the honeybee (Apis mellifera) [11]. However, a note of caution has been issued for individuals with allergies to crustaceans, mites, and mollusks, regarding the potential for adverse reactions triggered by insect proteins [67,68]. This finding underscores the need for continued research and highlights the potential risks associated with the consumption of edible insects.

Considering the available information on the allergenic potential of insects and the mechanisms of allergic reactions, including cross-reactions, two groups of individuals appear to be more susceptible: children and the elderly. In these populations, observed deficits in the gut microbiota have been implicated in reactions to food allergens. Therefore, in addition to genetic predisposition, specific characteristics and changes in their microbiota and physiology are likely to contribute to their increased susceptibility.

In infants and children, food allergy is the most prevalent form of allergic disease, frequently manifesting during the first four years of life. Significant changes in the microbiota of infants during the first year of life have been observed. These population shifts may be explained by factors including diet, the developing immune system, chemical exposures, and potential founder effects of initial colonizers [69]. The introduction of potentially highly allergenic foods is typically delayed until after the conclusion of the first year of life, recognizing the inherent immaturity of the infant mucosal immune system. This immaturity can impair the response of local immune cells to food antigens, contributing to an increased risk of food allergen sensitization.

Conversely, a growing body of research suggests that the recommendation for the early introduction of complementary foods, such as eggs, cow’s milk, and peanuts, after the fourth month of life, is based on the assumption of gradual exposure to known allergenic proteins [70]. These studies suggest that the early introduction of allergenic foods, ideally between 4 and 11 months of age, may help mitigate the development of food allergies in high-risk infants. However, the safety and practicality of this approach remain to be fully elucidated [71].

The initial infant gut microbiota is relatively simple, typically dominated by Bifidobacteria. Through a series of successions and replacements, it gradually transitions to a more complex adult-like pattern [72]. In the early years of life, a decline in the abundance of Bifidobacterium longum phylotype has been observed [73]. This decline parallels the decrease in Bifidobacteria that dominate fecal communities during this period [73].

Furthermore, the gastric fluid of newborns exhibits lower acidity, implying reduced pepsin activity [74]. This, in conjunction with lower concentrations of other digestive enzymes, may result in reduced proteolysis in the infant gastrointestinal tract compared to adults [74]. This reduced proteolysis may favor the maintenance of allergen stability within the organism, preserving the epitopes recognized by the immune system as allergenic.

A paucity of research has been conducted on the specific allergens present in edible insects and their potential to induce allergic reactions. Both food allergies and insect allergies can occur through various exposure routes, including inhalation, dermal contact, and ingestion [49].

Insects and their particles are ubiquitous in the environment. Despite the limited information available on allergies to edible insects, given the known mechanisms of food allergy, including cross-reactions, it is reasonable to hypothesize that sensitization to insects may also occur via dermal or inhalation routes, potentially promoting primary or secondary allergies in insect consumers.

There is consistent evidence of an association between food allergy and atopic dermatitis in children, often driven by either food sensitization or environmental allergens [75]. Thus, atopic individuals with a genetic predisposition to develop allergies through dermal contact may be at increased risk from exposure to edible insects.

As with the factors that promote allergies in children, there are even greater uncertainties regarding the factors that promote allergies in the elderly, due to a paucity of studies evaluating this situation. Few studies assess the increased susceptibility to allergies in the elderly. However, research on food allergies in this population remains scarce, despite their potential for persistence or re-emergence [76]. Allergies, including food allergies, are estimated to affect 5–10% of the elderly [76].

In aged skin, the skin barrier function may be compromised due to skin thinning, dryness, hyperkeratosis, and reduced production of hyaluronic acid and mucus. These changes can increase the risk of itching and skin infections, potentially complicating the diagnosis of allergic dermatitis. Despite a reduction in mucosal IgA, there is limited evidence directly linking IgA deficiency to food allergies in the elderly. However, IgA deficiency has been associated with various food intolerances and allergies [77].

It is hypothesized that age-related changes in systemic and local gastrointestinal mucosal immunity may increase the risk of primary or secondary food allergies following edible insect consumption [78]. Murine and human studies indicate that physiological changes affecting local immunity can contribute to food allergy development [79].

The composition of the adult intestinal microbiota demonstrates a pattern of stability. However, it has been demonstrated that disturbances to the gut environment, such as the use of antibiotics, have the capacity to temporarily impact this stability [69]. Following the depletion of microbial populations through antibiotic administration, a subsequent re-establishment of microbiota is observed, with 75 to 81% of the gut microbiota persisting for a minimum period of one year [80]. Furthermore, a proportion of 60% seems to persist for five years [81].

While mucosal tolerance, acquired in youth, may be maintained, de novo sensitization can occur with novel dietary proteins in aged individuals [82]. Furthermore, age-related IgA secretion decline alters the response to new antigens [83]. As the human body undergoes the process of aging, the gastrointestinal tract experiences a series of physiological changes that can impact the efficiency of food digestion and absorption, as well as immune function. A decline in the overall diversity of gut microbiota has been observed with advancing age, concurrent with the emergence of microbial taxa associated with accelerated aging [72]. The composition of the bacterial community is influenced by physiological variations along the gastrointestinal tract. For instance, fluctuations in acidity within the gastrointestinal tract have been demonstrated to disrupt the microbiota, potentially resulting in dysbiosis and contributing to an imbalance within the gut ecosystem [70,72], increasing susceptibility to allergic reactions in individuals sensitized by primary or cross-reaction.

The importance of diet in shaping the gut microbial community is highlighted by the observation that the transition to solid foods coincides with the establishment of a microbiota resembling the adult microbiota, comprising hundreds to thousands of species, dominated by the Bacteroidetes and Firmicutes phyla [69]. As the human body undergoes age-related changes, a decline in the diversity of Bacteroides and Bifidobacteria species has been observed. However, the proportion of the main bacterial phyla varies significantly between individuals and across geographical locations, emphasizing the crucial role of interactions between diet, environment, and lifestyle habits in shaping this variability [72].

A diet with high dietary diversity has been shown to influence allergy outcomes both directly, by supporting the development of a healthy gut microbiome, and indirectly, by providing nutrients with immunomodulatory properties [70]. Furthermore, differences in the microbiome have been observed to be associated with specific dietary patterns, such as the consumption of meat versus plant-based foods [73]. This observation underscores the pivotal role of dietary habits in maintaining intestinal homeostasis and potentially influencing the development of food sensitivities.

The evolution of food allergies in the elderly may exhibit variability due to the impact of aging on immunohistological and biochemical processes [84]. The immunological system is also subject to the effects of aging. Research on immunological memory indicates that older adults demonstrate a reduced response to vaccines, analogous to that observed in individuals with immunocompromised conditions [77]. Immunosenescence, a term encompassing the age-related changes in the immune system, involves alterations in both humoral and cellular immune responses in healthy individuals [85].

Micronutrient deficiencies, such as iron and vitamin D, prevalent in the elderly, also impair immune response and promote food allergies [86,87]. Micronutrient deficiency, commonly observed in the elderly, is recognized as a risk factor for the development of allergic disorders [78].

In elderly individuals, medication use is frequently observed, often due to the presence of comorbidities. Consequently, the manifestation of food allergy symptoms may be obscured by the increased use of these medications or even favored by the comorbidities. For instance, a decline in gastric acid production has been documented, predominantly in conjunction with Helicobacter pylori infection and atrophic gastritis. Concurrently, studies have demonstrated a correlation between age and pepsin output [88]. Both conditions may allow the allergenic protein to undergo less hydrolysis in the gastrointestinal tract, maintaining its characteristics that favor food allergy.

Lifestyle habits, particularly alcohol consumption, have been associated with sensitization to food allergens [89]. Furthermore, gastric hypoacidity, a condition prevalent in the elderly, may contribute to de novo sensitization by rendering harmless dietary compounds allergenic [78]. Common food allergens in adults include peanuts, nuts, fruits, vegetables, and seafood. Seafood allergy, notably, is a persistent condition, rarely resolved with age [90].

A further factor that can compromise the immune system is allergen sensitization, which initiates in the oral cavity where the digestive process begins. During mastication, food is physically fragmented and pre-digested by salivary enzymes. However, both the composition and production of saliva undergo age-related changes, potentially impacting this initial exposure to food antigens in the tonsils [91,92]. The elimination of this barrier has been shown to maintain the allergen in its original state, thereby enabling it to reach the intestine with its original allergenic potential. This phenomenon can be attributed to the fact that the allergen is no longer modified by the processes of mastication and the enzymes present in saliva, which have the potential to reduce its allergenicity.

An additional point to consider is that tonsillectomy, a prevalent surgical procedure, especially in early life, eliminates the primary defense mechanism against ingested and inhaled pathogens. Recent evidence suggests that alterations in immune pathways in early life, including dysbiosis, may have long-lasting effects on adult health. A strong association has been found between the removal of immune organs in the upper respiratory tract during childhood and an increased risk of infectious and parasitic diseases manifesting later in life. Specifically, tonsillectomy has been associated with a nearly threefold relative risk of upper respiratory tract disease, while adenoidectomy has been associated with a more than twofold relative risk of chronic obstructive pulmonary disease and a nearly twofold relative risk of upper respiratory tract disease [92]. Despite this, the long-term impact of tonsillectomy and adenoidectomy on the potential for allergy development in older people has not yet been assessed, taking into account the sum of other ageing characteristics that increase their vulnerability to allergy.

Therefore, both groups exhibit allergen interaction mechanisms that may increase susceptibility to edible insect allergies, particularly in children and the elderly, due to their distinct immune system and gut microbiota characteristics. In fact, the specific frequency of food allergy is higher in children than in adults [93], and between 5 and 10% of allergic diseases affect the elderly [94]. However, few studies describe food allergy in these specific populations because of their differences from other age groups. To the best of my knowledge, none are specific to edible insect allergy.

5. Conclusions

This review highlights the role of the gut microbiome and the fate of food allergens throughout the digestive tract in the development of allergy symptoms as important components of the increased susceptibility of young children and the elderly. More than other age groups, children and the elderly have age-related differences in their microbiota and digestive and immune system characteristics that increase their susceptibility to food allergens.

The existence of a specific group of bacteria or their association in the microbiota that can effectively protect the organism against the immune response needs to be better understood. It is conceivable that moderate exposure to allergens during early life may contribute to an individual’s resistance by promoting an adapted microbiota. Similarly, age-related changes, such as a decline in protective microorganisms, may contribute to the manifestation or development of food allergy reactions, in conjunction with other age-related physiological changes. However, the paucity of available data precludes any conclusions regarding the behavior of these organisms when faced with the challenge of ingesting allergenic proteins from edible insects. Nevertheless, there are components that increase the susceptibility of these age groups to other allergens, suggesting that edible insects also have a higher risk of causing allergic reactions in these groups.

The incorporation of edible insect protein into processed food products necessitates a comprehensive global safety evaluation. This assessment must rigorously address the nutritional, toxicological, and allergenic potential of these foods, with a specific focus on consumer safety. A critical challenge lies in the precise identification and characterization of allergens within diverse edible insect species. Achieving this objective necessitates a thorough understanding of the insect microbiota and its associated protein expression, which is essential prior to widespread dietary integration.