Food-Grade Silicon Dioxide Nanoparticles Disrupt the Microbiota-Associated Gut–Liver Axis and FXR-Related Bile Acid Homeostasis in Mice

Food-grade silica (E551) is widely used as an anticaking additive, raising concerns about repeated exposure to nanoscale silica fractions. However, its long-term effects on microbiota-associated gut–liver regulation and FXR-related bile acid homeostasis remain unclear. Male C57BL/6J mice were fed control or SiO2NP-containing diets providing 225, 1000, or 5000 mg/kg bw/day for 8 weeks. SiO2NP exposure induced colonic barrier injury and elevated circulating lipopolysaccharide levels. Fecal microbiota profiling of the NC and high-dose groups revealed compositional alterations associated with high-dose exposure. In parallel, intestinal and hepatic FXR-related marker expression was reduced, while the expression of genes involved in bile acid synthesis and transport was altered. Exposed mice also showed elevated serum total bile acid levels and liver injury with inflammatory, lipid metabolic, and fibrotic responses. These findings suggest that chronic oral SiO2NP exposure disturbs intestinal and hepatic homeostasis, potentially involving FXR-related bile acid dysregulation along the gut–liver axis.