Background and Aim: The worldwide prevalence of food sensitivities, including food allergies and autoimmune conditions, such as celiac disease (CeD), has increased in the past decades. This suggests that co-factors, linked to industrialization, are involved. One understudied factor typically used in processed foods and considered harmless, are inorganic nanoparticles (NPs). Our aim was to investigate whether daily exposure to the NP-structured silicon dioxide (SiO ), employed as an anticaking agent in powdered foods, including infant formula, alters oral tolerance (OT) induction to ovalbumin (OVA), and increases severity of gluten sensitivity in mice. Methods: An OT induction model to OVA was used in C57BL/6J mice that were orally exposed to food-grade (fg) SiO for 60 days (10mg/kg body weight/day) in water suspension (gastric gavage) or incorporated into food pellets (solid matrix). Controls were gavaged with water. The gut immune response and immune cell populations induced were analysed by flow cytometry. Non-obese diabetic (NOD) mice expressing the CeD susceptibility gene HLA-DQ8 (NOD/DQ8) were exposed to fg-SiO , and subsequently immunized with gluten, the main environmental trigger of CeD. Small intestinal immunopathology was investigated at endpoint through assessment of villus-to-crypt ratios and intraepithelial lymphocyte (IEL) counts. Results: fg-SiO at human dietary levels led to low-grade intestinal inflammation evidenced by higher proinflammatory cytokines, such as IFN-γ, and lower anti-inflammatory cytokines, including IL-10 and TGF-β, known mediators in OT. After OT induction to OVA, fg-SiO exposure was associated with decreased expansion of IL-10 and TGF-β-producing T cells and the development of a pro-inflammatory Th1 inflammatory response. fg-SiO exposure through gastric gavage, but not through food pellets, decreased the frequency of CD103 dendritic cells. In NOD/DQ8 mice, fg-SiO decreased villus-to-crypt ratios, increased IELs counts, and enhanced the Th1 inflammatory response induced by immunization to gluten. Conclusions: Chronic oral exposure to the food additive SiO blocked the establishment of OT in the gut leading to intestinal inflammation and worsening of gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between SiO exposure and food sensitivities in humans.