Evaluating the Effects of Chronic Oral Exposure to the Food Additive Silicon Dioxide on Oral Tolerance Induction and Food Sensitivities in Mice.

Background: The increasing prevalence of food sensitivities has been attributed to changes in gut microenvironment; however, ubiquitous environmental triggers such as inorganic nanoparticles (NPs) used as food additives have not been thoroughly investigated.
Objectives: We explored the impact of the NP-structured food-grade silicon dioxide ( f g - SiO 2 ) on intestinal immune response involved in oral tolerance (OT) induction and evaluated the consequences of oral chronic exposure to this food-additive using a mouse model of OT to ovalbumin (OVA) and on gluten immunopathology in mice expressing the celiac disease risk gene, HLA-DQ8.
Methods: Viability, proliferation, and cytokine production of mesenteric lymph node (MLN) cells were evaluated after exposure to f g - SiO 2 . C57BL/6J mice and a mouse model of OT to OVA were orally exposed to f g - SiO 2 or vehicle for 60 d. Fecal lipocalin-2 (Lcn-2), anti-OVA IgG, cytokine production, and immune cell populations were analyzed. Nonobese diabetic (NOD) mice expressing HLA-DQ8 (NOD/DQ8), exposed to f g - SiO 2 or vehicle, were immunized with gluten and immunopathology was investigated.
Results: MLN cells exposed to f g - SiO 2 presented less proliferative T cells and lower secretion of interleukin 10 (IL-10) and transforming growth factor beta ( TGF- β ) by T regulatory and CD 45 + CD 11 b + CD 103 + cells compared to control, two factors mediating OT. Mice given f g - SiO 2 exhibited intestinal Lcn-2 level and interferon gamma ( IFN- γ ) secretion, showing inflammation and less production of IL-10 and TGF- β . These effects were also observed in OVA-tolerized mice exposed to f g - SiO 2 , in addition to a breakdown of OT and a lower intestinal frequency of T cells. In NOD/DQ8 mice immunized with gluten, the villus-to-crypt ratio was decreased while the CD 3 + intraepithelial lymphocyte counts and the Th1 inflammatory response were aggravated after f g - SiO 2 treatment.
Discussion: Our results suggest that chronic oral exposure to f g - SiO 2 blocked oral tolerance induction to OVA, and worsened gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between SiO 2 exposure and food sensitivities in humans. https://doi.org/10.1289/EHP12758.