Silicon dioxide nanoparticles induced neurobehavioral impairments by disrupting microbiota-gut-brain axis.

ABSTRACT

BACKGROUND: Silicon dioxide nanoparticles (SiO2NPs) are widely used as additive in the food industry with controversial health risk. Gut microbiota is a new and hot topic in the field of nanotoxicity. It also contributes a novel and insightful view to understand the potential health risk of food-grade SiO2NPs in children, who are susceptible to the toxic effects of nanoparticles. METHODS: In current study, the young mice were orally administrated with vehicle or SiO2NPs solution for 28 days. The effects of SiO2NPs on the gut microbiota were detected by 16S ribosomal RNA (rRNA) gene sequencing, and the neurobehavioral functions were evaluated by open field test and Morris water maze. The level of inflammation, tissue integrity of gut and the classical indicators involved in gut-brain, gut-liver and gut-lung axis were all assessed. RESULTS: Our results demonstrated that SiO2NPs significantly caused the spatial learning and memory impairments and locomotor inhibition. Although SiO2NPs did not trigger evident intestinal or neuronal inflammation, they remarkably damaged the tissue integrity. The microbial diversity within the gut was unexpectedly enhanced in SiO2NPs-treated mice, mainly manifested by the increased abundances of Firmicutes and Patescibacteria. Intriguingly, we demonstrated for the first time that the neurobehavioral impairments and brain damages induced by SiO2NPs might be distinctively associated with the disruption of gut-brain axis by specific chemical substances originated from gut, such as Vipr1 and Sstr2. Unapparent changes in liver or lung tissues further suggested the absence of gut-liver axis or gut-lung axis regulation upon oral SiO2NPs exposure. CONCLUSION: This study provides a novel idea that the SiO2NPs induced neurotoxic effects may occur through distinctive gut-brain axis, showing no significant impact on either gut-lung axis or gut-liver axis. These findings raise the exciting prospect that maintenance and coordination of gastrointestinal functions may be critical for protection against the neurotoxicity of infant foodborne SiO2NPs.