The gut immune system is daily exposed to inorganic particles used as food additives or processing aids in the food industry, such as silicon dioxide (SiO2), a common anticaking agent in manufacturing powdered foods (milk, infant formulae, instant soups), ingredients (spices, salt, flours) and supplements. In mucosal surfaces like the gut, a state of unresponsiveness to non-self antigens, called oral tolerance (OT), is established to prevent sensitivities, such as food allergies (peanuts, seafood) and autoimmune conditions driven by gluten proteins, namely, celiac disease (CeD). Here we investigated whether long-term oral exposure to food-grade (fg) SiO2 alters the intestinal immune response involved in OT, and the consequences in a model of gluten sensitivity. Wild type mice (C57BL/6) were daily treated for 60 days with fg-SiO2 (10mg/kg body weight/day) in water suspension (gastric gavage) or incorporated into food pellets (solid matrix). Controls received only water. The gut immune response and OT induction to a food antigen model (ovalbumin, OVA) were evaluated, and intestinal immune cell populations analysed by flow cytometry. In addition, non-obese diabetic (NOD) mice expressing the CeD susceptibility gene DQ8 and exposed to fg-SiO2 were sensitized to gluten. Development of small intestinal immunopathology was assessed at sacrifice. Chronic oral exposure to fg-SiO2 at human dietary levels, triggers low-grade intestinal inflammation evidenced by increased production of the pro-inflammatory cytokines IFN-γ, and decreased production of the anti-inflammatory cytokines IL-10 and TGF-β, key mediators of OT. After OT induction to OVA, fg-SiO2 exposure decreased the frequency of IL-10 and TGF-β producing T cells, leading to breakdown of OT and mucosal inflammation. fg-SiO2 exposure through gastric gavage, but not through food pellets, decreased the frequency of CD103+ dendritic cells. Using water as fg-SiO2 vehicle, gluten immunopathology was worsened in NOD/DQ8 mice, characterized by decreased villus-to-crypt ratios, increased CD3+ IELs counts, and an enhanced Th1 inflammatory response. These data collectively show that chronic, daily oral exposure to food-grade SiO2 particles blocked the establishment of OT in the gut, inducing intestinal inflammation worsening the development of gluten sensitivity in a mouse model of CeD. This raises the hypothesis that chronic exposure to SiO2 through the diet could act as environmental trigger of loss of tolerance in genetically susceptible people and lead to onset of food sensitivities. Our results should encourage epidemiological research on potential adverse effects related to the chronic intake of food additive SiO2 in particular, its association with food allergies and autoimmune conditions, such as celiac disease.