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

Environmental contamination with TiO2 and the use of TiO2 as a food additive (E171) or in cosmetics result in human exposure to TiO2 via 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.