Editorial: "Role of nanoparticles in the development and severity food allergy"

Angela Rizzi^1*Sebastiano Gangemi²

• ¹UOSD Allergologia e Immunologia Clinica, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy
• ²Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology , University of Messina, 98125, Messina, Italy

Food allergy, inappropriate immune response against dietary antigens, is a multifactorial condition with increased incidence not only in industrialized countries but also in developing ones (1). Although there are still doubts about the exact causes and pathogenic mechanisms, it is now widely known that the progression towards damage to the intestinal epithelial barrier is influenced by the intricate relationship between genetic susceptibility, environmental and immunological factors (2). Among the environmental factors to which humans are unintentionally exposed in everyday life through the diet, there are inorganic dietary nanoparticles (IDNPs) ranging from 1 to100 nanometres as titanium dioxide (TiO2NP or E171), zinc oxide (ZnONP), or silver (AgNP or E174) nanoparticles. All the material in the "nano" size present new exciting chemo-physical properties compared to their conventional bulk counterparties that can be useful in several applications. For this reason, nanomaterials are today used in a wide range of applications, from agriculture and sustainable energy to food chain and medical applications (3). Although studies on the gastrointestinal tract are scanty, it has been shown that nanoparticles can alter intestinal homeostasis and permeability by compromising the epithelial barrier and, in turn, activate the innate and adaptive immune response, possibly also affecting the gut microbiota. This could be relevant for patients with immuno-allergic diseases, such as those with inflammatory bowel disease (IBD) or food allergies (4-5). This special issue comprehensively describes several aspects of food allergies. Starting from the report of the prevalence of this condition in Latin America, the Special Issue moves to different pathogenetic mechanisms of damage underlining the genesis of food allergy: a translational animal model of α-Gal/red meat allergy based on gene-deficiency and an in vitro and animal study of intestinal barrier impairment due to the co-exposure with allergen and bacterial enterotoxins. An in-depth narrative review describes the effects of exposure to inorganic nanoparticles on the intestinal barrier and consequent potential pathogenic role in IBD. Readers will find four contributions in this special issue: three original articles and one review article, accessible here: www.frontiersin.org/research-topics/65925/impact-of-dietary-nanoparticles-on-food-allergy-development-and-immune-response (accessed on 21 August 2025). Olaya-Hernández et al. conducted one of the few epidemiological studies on food allergy in Latin America, which, due to the tropical and subtropical climate, high cultural diversity, and diverse food preparation methods, represents the most common cause of anaphylaxis (6,7). For the first time, this study explores the prevalence and clinical characteristics of food allergy confirmed by oral challenge in a cohort of 176 Colombians. The population was predominantly paediatrics, with a mean age of two years. Surprisingly, no sensitization was found to tropical fruits but rather to eggs, shellfish, and cow's milk, tested through skin tests and specific IgE. The positive rate for oral challenge was 5.5% (only 12 patients): five patients with cow's milk, five with shrimp and two with legumes. Wang et al. chose the porcine model to better understand the pathogenic mechanisms underlying food allergy, and particularly α-Gal allergy, starting from the assumption that this animal reflects human intestinal physiology, anatomy and immune system much more faithfully than the murine model, already widely used by researchers (8). Previously, both peanut allergy (9-10) and egg allergy (11) were investigated with the same animal model. To sensitize the animals in a way that mimics tick bites in humans as closely as possible, the Authors preferred repeated intracutaneous injections of α-Gal to the "tape stripping" method, which mechanically compromises the porcine skin barrier with major stress to the animal. Consequently, these sensitized animals showed a clear cutaneous and serum allergic response with an increase in T helper 2 (Th2) cells and increase in proallergic cytokines and epithelial-derived alarmins. Similarly, an increase in Th1 cells was observed, capable of triggering further inflammatory responses. Finally, re-exposure of pre-sensitized pigs to α-Gal also reproduced anaphylaxis with mediator release, fully confirming the animal model. The in vivo and in vitro study conducted by Chinese researchers led by Yaun also focuses on the same goal: better understanding of the role of environmental factors such as bacterial enterotoxins in the development of food allergies. Interestingly, oral exposure to even low doses of Staphylococcus aureus enterotoxin B (SEB) in ovalbumin (OVA)-sensitized mice appears to be a significant risk factor for the development and severity of food allergy. Indeed, histopathological analyses revealed that the intestinal barrier of mice simultaneously exposed to OVA and SEB was disrupted compared to OVA group, with loss of goblet cells, damaged epithelium, and overall tissue architecture distortion. Furthermore, real-time PCR analyses showed reduced expression of tight junction proteins (claudin-2, Occludin, and ZO-1) in the OVA + high SEB group, as well as more Th2 polarization (more IL-13 and less IFN-γ) in mice co-exposed to low doses of SEB, again compared to the OVA-only group. Similarly, in vitro studies using cell co-culture models have shown that co-exposure to SEB and OVA plays a crucial role in the development of food allergy because it accelerates the activation of dendritic cells, allowing for increased allergen uptake and its presentation by bone marrow dendritic cells to T cells for upregulation of genes involved in immune responses. Additionally, exposure to SEB causes a partial reduction in caecal flora biodiversity in OVA-sensitized mice. Like food allergy, the prevalence of IBD has risen in industrialized countries with increasing consumption of junk food and food additives containing various IDNPs. The closing paper by Luo et al. exhaustively reviews the role and potential immunopathological mechanisms of these environmental factors in the development of IBD with a focus on the intestinal barrier in terms of physical, chemical, biological, and immune barriers. Notoriously, the function of IDNPs in the body is quite intricate. While it is influenced by the shape, size, composition, surface properties, and state of aggregation of the nanoparticles themselves, the formation of a biological corona around the nanoparticles when they come into contact with various food ingredients or intrinsic components of the gastrointestinal tract (proteins, lipids, carbohydrates, etc.) can in turn alter the biocompatibility of the nanoparticles, altering their absorption and thus their toxicity. Although a growing body of literature has explored these aspects, research findings are often conflicting and lacking definitive conclusions. This may be due to methodological differences, such as differences in species, sex, age, and feeding habits of the animals, or the intrinsic characteristics of the IDNPs chosen, or even to drug use, pre-existing conditions, or disease activity. Secondly, there are a limited number of in vivo studies on the chronic toxicity of IDNPs, to which living beings are likely increasingly exposed over the long term. Similarly, there are no relevant studies investigating exposure levels and the effects of IDNPs in food packaging on humans without a unified standard for toxicity monitoring. Conclusion We sincerely thank all authors who submitted their articles and the reviewers who took the time to review them. As an editorial team, we hope this special issue offers valuable insights for a better understanding of the epidemiological and pathophysiological aspects of immune-allergic diseases.