Dietary metallic nanoparticles: a new environmental factor in the development od Celiac Disease?

The recent application of nanotechnology in several fields has brought big improvements, but also a big question about their safety for humans. Particularly worrisome is the use of a great amount of metallic nanoparticles (mNPs) in food industry to improve food taste, consistency and preservation. Previous studies have demonstrated that they can impair intestinal homeostasis inducing cytotoxic damage, altering the permeability and activating autophagic processes. Moreover, they can interact with the immune system, causing different immunomodulatory effects. Since all these processes are involved in the development of celiac disease (CeD), a multifactorial enteropathy caused by dietary gliadin ingestion, we speculate that mNP may be one of the environmental factors involved in the increased incidence of this disease. Therefore we evaluated the potential interaction and synergic effects of the most used mNP (TiO2-NP used as food coloring agent, ZnO- and Ag-NP used for their antimicrobial effects and AuNP used in the agro-food sector) with the peptic-triptic digested gliadin (PTG) using several intestinal models. Cytotoxic effects and permeability alterations were studied on CaCo2 intestinal cell line, autophagic induction was evaluated on HIEC cells (primary human crypt-like epithelial cells). To evaluate the immune response, we employed duodenal biopsy specimens from both healthy subjects and celiac patients (on gluten-free diet). To characterize the morphological tissue changes we performed organs culture studies on jejunum from human fetus at mid-gestation (17-19 weeks). Results showed worse effects when mNP were used in combination with the PTG, in all the used models. Particularly important are the data showing a significant increment in cytokines production after treatment with the combination of Au-, Ag- and TiO2-NP with PTG on biopsies from celiac patients, but not from healthy subjects. This could mean that, although the use of mNP in the food industry induces really slight toxic effect on healthy people, it could be harmful for patients genetically predisposed to develop intestinal diseases. Despite further studies are necessary to better characterize the role of food mNPs on the development of celiac disease, our data proved an interaction and a combined deleterious effect of mNP with PTG, leading to the hypothesis that these food additives could increase the percentage of predisposed individuals developing CeD.

Sebbene l'uso di nanomateriali sta crescendo, non è ancora stato capito se rappresenti un rischio per la nostra salute. Particolarmente, l'uso di nanoparticelle nell'industria alimentare è preoccupante. Infatti, differenti gruppi di ricerca hanno dimostrato che, particolarmente le nanoparticelle metalliche, possono alterare l'omeostasi intestinale. Conseguentemente potrebbero rappresentare un fattore di rischio nell'insorgenza di patologie infiammatorie intestinali, come la Celiachia. La Celiacha è una patologia autoimmune che si sviluppa in soggetti geneticamente predisposti, dopo l'ingestione di glutine. Considerando queste premesse, lo scopo del nostro lavoro è capire se il crescente uso di nanoparticelle alimentari possa avere un ruolo nell’ eziopatogenesi della Celiachia. Gli effetti di nanoparticelle alimentari con o senza glutine sono quindi stati studiati in differenti modelli che mimano l’intestino. Risultati hanno evidenziato che la stimolazioni con glutine e nanoparticelle alimentari inducono peggiori effetti che le singole componenti. Tutte le alterazioni ottenute potrebbero comportare l’instaurarsi della Celiachia in un numero maggiore di soggetti predisposti, suggerendo che l’uso di nanoparticelle nell’industria alimentare dovrebbe essere maggiormente controllato.