No abstract

Celiac disease (CeD) is a multifactorial autoimmune disorder spread worldwide. The exposure to gluten, a protein found in cereals like wheat, barley and rye, is the main environmental factor involved in its pathogenesis. Even if the genetic predisposition represented by HLA-DQ2 or HLA-DQ8 haplotypes is widely recognised as mandatory for CeD development, it is not enough to explain the total predisposition for the disease. Furthermore, the onset of CeD comprehend a wide spectrum of symptoms, that often leads to a delay in CeD diagnosis. To overcome this deficiency and help detecting people with increased risk for CeD, also clarifying CeD traits linked to disease familiarity, different studies have tried to make light on other predisposing elements. These were in many cases genetic variants shared with other autoimmune diseases. Since inherited traits can be regulated by epigenetic modifications, also induced by environmental factors, the most recent studies focused on the potential involvement of epigenetics in CeD. Epigenetic factors can in fact modulate gene expression with many mechanisms, generating more or less stable changes in gene expression without affecting the DNA sequence. Here we analyze the different epigenetic modifications in CeD, in particular DNA methylation, histone modifications, non-coding RNAs and RNA methylation. Special attention is dedicated to the additional predispositions to CeD, the involvement of epigenetics in developing CeD complications, the pathogenic pathways modulated by epigenetic factors such as microRNAs and the potential use of epigenetic profiling as biomarker to discriminate different classes of patients.

The use of nanoparticles (NPs) has surely grown in recent years due to their versatility, with a spectrum of applications that range from nanomedicine to the food industry. Recent research focuses on the development of NPs for the oral administration route rather than the intravenous one, placing the interactions between NPs and the intestine at the centre of the attention. This allows the NPs functionalization to exploit the different characteristics of the digestive tract, such as the different pH, the intestinal mucus layer, or the intestinal absorption capacity. On the other hand, these same characteristics can represent a problem for their complexity, also considering the potential interactions with the food matrix or the microbiota. This review intends to give a comprehensive look into three main branches of NPs delivery through the oral route: the functionalization of NPs drug carriers for systemic targets, with the case of insulin carriers as an example; NPs for the delivery of drugs locally active in the intestine, for the treatment of inflammatory bowel diseases and colon cancer; finally, the potential concerns and side effects of the accidental and uncontrolled exposure to NPs employed as food additives, with focus on E171 (titanium dioxide) and E174 (silver NPs).

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV–Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.