Journal Article

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

Verdu, Elena F., Martins Breyner, Natalia, Houdeau, Eric, Wulczynski, Mark, Cartier, Christel, Lamas, Bruno, Malaisé, Yann, Gaultier, Eric, Galipeau, Heather J.

2024

Overview

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. We explored the impact of the NP-structured food-grade silicon dioxide ( ) 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. Viability, proliferation, and cytokine production of mesenteric lymph node (MLN) cells were evaluated after exposure to . C57BL/6J mice and a mouse model of OT to OVA were orally exposed to 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 or vehicle, were immunized with gluten and immunopathology was investigated. MLN cells exposed to presented less proliferative T cells and lower secretion of interleukin 10 (IL-10) and transforming growth factor beta ( ) by T regulatory and cells compared to control, two factors mediating OT. Mice given exhibited intestinal Lcn-2 level and interferon gamma ( ) secretion, showing inflammation and less production of IL-10 and . These effects were also observed in OVA-tolerized mice exposed to , 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 intraepithelial lymphocyte counts and the Th1 inflammatory response were aggravated after treatment. Our results suggest that chronic oral exposure to blocked oral tolerance induction to OVA, and worsened gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between exposure and food sensitivities in humans. https://doi.org/10.1289/EHP12758.

• Publisher: National Institute of Environmental Health Sciences,Environmental Health Perspectives
• Subject: Additives / Administration, Oral / Animals / Autoimmune diseases / CD103 antigen / CD11b antigen / CD3 antigen / CD45 antigen / Celiac disease / Cell proliferation / Chemical properties / Chronic exposure / Cytokines / Development and progression / Diabetes mellitus / Environmental aspects / Enzymes / Exposure / Food additives / Food Additives - pharmacology / Food allergy / Gastrointestinal system / Gluten / Glutens - pharmacology / Growth factors / Health aspects / Health risks / Histocompatibility antigen HLA / Humans / Immune response / Immune system / Immune Tolerance - genetics / Immunization / Immunoglobulin G / Immunological tolerance / Inflammation / Inflammatory response / Interferon / Interleukin 10 / Interleukin-10 - pharmacology / Intestine / Investigations / Lipocalin / Lymph nodes / Lymphocytes / Lymphocytes T / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Microbiota / Microenvironments / Nanoparticles / Open source software / Ovalbumin / Ovalbumin - pharmacology / Physiological aspects / Risk factors / Silica / Silicon / Silicon dioxide / Silicon Dioxide - toxicity / Transforming growth factor-b / Villus