A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice
Background: Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cakes decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact on human health of mineral particles used as food additives are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were daily exposed for 90 days to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose levels to determine the potential toxicity of the edible gold. Results: E175 or Ref-Au exposure in mice did not induce any histomorphological damage in the liver, spleen or intestine or any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No alterations in the intestinal microbiota were observed after exposure to Ref-Au. However, following E175 treatment, a more marked alteration in the gut microbiota characterized by an increased Firmicutes/Bacteroidetes ratio and Proteobacteria abundance as well as a decreased production of short-chain fatty acids (SCFAs) was noticed in female mice compared to males. Moreover, increased production of IL-6, TNFa and IL-1ß was observed in the colon of female mice at the end of the 90-day exposure to E175, while in contrast, decreased IL-6, IL-1ß, IL-17 and TGFß levels were found in the male colon. Conclusions: Results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.