Titanium dioxide nanoparticles via oral exposure leads to adverse disturbance of gut microecology and locomotor activity in adult mice.

Titanium dioxide nanoparticles (TiO2NPs) have been widely used as food additives in daily life. However, the impact of oral intake of TiO2NPs on the nervous system is largely unknown. In this study, 7-week-old mice were treated with either vehicle or TiO2NPs suspension solution at 150 mg/kg by intragastric administration for 30 days. Our results demonstrated that oral exposure to TiO2NPs resulted in aberrant excitement of enteric neurons, although unapparent pathological changes were observed in gut. We also found the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed in the TiO2NP-treated group as compared with vehicle controls. Interestingly, oral exposure to TiO2NPs was capable to induce the inhibitory effects on locomotor activity, but it did not lead to significant change on the spatial learning and memory ability. We further revealed the mechanism that TiO2NPs could specifically cause locomotor dysfunction by elevating the excitement of enteric neuron, which might spread to brain via gut-brain communication by vagal pathway. However, inflammation response, enteric neurotransmitter 5-HT and major gut peptides might not be involved in this pathological process. Together, these findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.