Dietary nanoparticles compromise epithelial integrity and enhance translocation and antigenicity of milk proteins: An in vitro investigation

Abstract

Nanoparticles (NPs) are increasingly being used in the food sector, yet little is known about the potential health risks associated with oral exposure to dietary NPs. In this study, the most widely used NPs in food industry including food grade silicon dioxide (SiO2), titanium dioxide (TiO2) and silver (Ag), along with their non-food grade and bulk counterparts, are characterized for physicochemical properties and molecular, cellular, and intracellular effects on human intestinal epithelial cells (Caco-2 and HIEC-6). Silver NPs are the most cytotoxic and induce significant cellular changes in oxidative stress, Ca2+ flux and mitochondria function, leading to cellular junction disruption at the lowest exposure concentration. At higher testing concentrations, NPs but not microparticles of SiO2 and TiO2 cause sublethal cellular responses and remodel tight junctions without impairing epithelial integrity. To relate the cellular results to key events in GI disorder progression, NPs are exposed to an in vitro co-culture model for cow's milk allergy comprised of Caco-2 and allergy sera-primed mast cells (LUVA). All particle treatments increase the allergen delivery across intestinal epithelium and subsequent allergy responses. Overall, the study has identified a particle-dependent alteration in intestinal epithelium and highlighted potential safety concerns of dietary NPs.