The food additive titanium dioxide hinders intestinal production of TGF-β and IL-10 in mice, and long-term exposure in adults or from perinatal life blocks oral tolerance to ovalbumin

Food hypersensitivities are increasing in industrialized countries, and foodborne nanoparticles (NPs) are suspected as co-factors in their aetiology. Food-grade titanium dioxide (fg-TiO₂), a food colouring agent, is composed of NPs with immunomodulatory properties. We investigated whether fg-TiO₂ may compromise the establishment of oral tolerance (OT) to food proteins using a model of OT induction to ovalbumin (OVA) in mice, and whether a perinatal exposure could trigger this effect. In pregnant mice fed a TiO₂-enriched diet, ICP-MS and TEM-EDX analyses showed passage of TiO₂ NPs into the foetus. When their weaned offspring were fed the same diet, a breakdown in OT to OVA was observed at adulthood, characterized by a high anti-OVA IgG production compared to controls. However, adult mice directly exposed to fg-TiO₂ did not induce OT to OVA either, ruling out a developmental origin for these effects. When these mice were orally challenged with OVA, intestinal inflammation demonstrated hypersensitivity to OVA. In OVA-naïve mice, fg-TiO₂ exposure impaired intestinal TGF-β and IL-10 production, of key role in OT induction and maintenance. These findings showed that long-term exposure to TiO₂ as food additive alters anti-inflammatory cytokine profile, and leads to OT failure regardless of the timing of TiO₂ exposure throughout life.