The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro

Abstract

Environmental contamination with TiO₂ and the use of TiO₂ as a food additive (E171) or in cosmetics result in human exposure to TiO₂via inhalation, ingestion, and through skin contact. When inhaled, most TiO₂ particles are cleared via the mucociliary escalator and are then swallowed. Together with the ingestion of E171, this process results in a significant exposure of the human gastro-intestinal tract to TiO₂. One of the functions of the intestine is to protect the body from external aggression, via the so-called intestinal barrier function. The aim of this study was to determine whether, and through which mechanisms, TiO₂ affects this function. Caco-2 and HT29-MTX cells were co-cultured to reconstitute an in vitro mucus-secreting intestinal epithelium. This epithelium was exposed to TiO₂-NPs, either pure anatase or mixed anatase/rutile, or to E171. Two exposure scenarii were used: acute exposure for 6 h or 48 h after cell differentiation (21 days post-seeding), or repeated exposure during the course of cell differentiation, i.e., twice a week for 21 days post-seeding. Epithelial cells repeatedly exposed to TiO₂ developed an inflammatory profile, together with increased mucus secretion. Epithelial integrity was unaltered, but the content of ATP-binding cassette (ABC) family xenobiotic efflux pumps was modified. Taken together, these data show that TiO₂ moderately but significantly dysregulates several features that contribute to the protective function of the intestine.