Fig. 8

The toxic pathway of hepatotoxicity induced by oral exposure to TiO₂ NPs through lipid metabolism disorders in gut-liver axis. Due to limited intestinal absorption and strong oxidation induction ability of TiO₂ NPs, the gut microbiota was presumed to be the original site of oxidative stress and disorders of lipid metabolism. In fact, TiO₂ NPs changed lipidomic signatures of main organs or systems in the gut-liver axis including liver, serum and gut. The cluster profile from the above biological samples all pointed to the same key metabolic pathway and metabolites, which was glycerophospholipid metabolism and Phosphatidylcholines (PCs), respectively. Lipid peroxidation characterized by the increase of malondialdehyde (MDA) may be the initial step of lipid metabolism disorders, which resulted in hepatic fatty degeneration and liver function changes, leading to hepatotoxicity. Most nanomaterials (NMs) have oxidation induction and antibacterial properties, so this toxic pathway may be primary and universal