Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake 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 of mineral particles used as food additives on human health 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 exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold. E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor 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 changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1β was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1β, IL-17 and TGFβ levels were found in the male colon. These 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 observed 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.

中文翻译：

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小鼠口服相关人体剂量的食品级黄金 90 天后，会以性别依赖性方式影响肠道微生物群和局部免疫系统

食用金 (Au) 通常用作食品添加剂（欧盟为 E175），用于糖果和蛋糕装饰、涂层和饮料。食品级金通常由薄金片或薄片组成，其厚度具有微米和纳米尺寸。由于纳米颗粒的特殊理化性质，矿物颗粒用作食品添加剂对人类健康的影响日益受到关注，纳米颗粒使它们能够跨越生物屏障并与各种人体细胞区室相互作用。在这项研究中，雄性和雌性小鼠每天接触 E175 或以相关人类剂量掺入食物中的金纳米材料 (Ref-Au)，持续 90 天，以确定食用金的潜在毒性。小鼠中 E175 或 Ref-Au 暴露不会引起任何肝脏组织形态学损伤，尽管与 E175 食品添加剂相比，暴露于 Ref-Au 的小鼠肠道对 Au 颗粒的吸收水平明显更高，但对脾脏或肠道没有任何遗传毒性作用，对结肠和肝脏也没有任何遗传毒性作用。无论性别如何，Ref-Au 治疗后肠道微生物群均未发生变化。相比之下，暴露于 E175 后，在雌性中观察到厚壁菌门/拟杆菌门比率和变形菌门丰度增加，而两性的短链脂肪酸产量均减少。此外，在暴露于 E175 90 天结束时，观察到雌性小鼠结肠中 IL-6、TNFα 和 IL-1β 的产生增加，而 IL-6、IL-1β、IL-17 和 TGFβ 的产生减少在男性结肠中发现了水平。这些结果表明，小鼠在饮食中添加 E175 90 天后，会以性别依赖性方式改变肠道微生物群和肠道免疫反应。在人类暴露于 E175 的剂量范围内，这些变化在两性中仍然很低，并且大多数似乎是无毒的。然而，在较高剂量下，观察到的雌性小鼠肠道菌群失调和肠道低度炎症可能有利于代谢紊乱的发生，支持建立安全使用金作为食品添加剂的毒性参考值。