Landscape of lipidomic metabolites in gut-liver axis of Sprague–Dawley rats after oral exposure to titanium dioxide nanoparticles

BACKGROUND: The application of titanium dioxide nanoparticles (TiO(2) NPs) as food additives poses a risk of oral exposure that may lead to adverse health effects. Even though the substantial evidence supported liver as the target organ of TiO(2) NPs via oral exposure, the mechanism of liver toxicity remains largely unknown. Since the liver is a key organ for lipid metabolism, this study focused on the landscape of lipidomic metabolites in gut-liver axis of Sprague Dawley (SD) rats exposed to TiO(2) NPs at 0, 2, 10, 50 mg/kg body weight per day for 90 days. RESULTS: TiO(2) NPs (50 mg/kg) caused slight hepatotoxicity and 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. In addition, absolute quantitative lipidomics verified the changes of three PCs concentrations, including PC (16:0/20:1), PC (18:0/18:0) and PC (18:2/20:2) in the serum samples after treatment of TiO(2) NPs (50 mg/kg). The contents of malondialdehyde (MDA) in serum and liver increased significantly, which were positively correlated with most differential lipophilic metabolites. CONCLUSIONS: The gut was presumed to be the original site of oxidative stress and disorder of lipid metabolism, which resulted in hepatotoxicity through the gut-liver axis. Lipid peroxidation may be the initial step of lipid metabolism disorder induced by TiO(2) NPs. Most nanomaterials (NMs) have oxidation induction and antibacterial properties, so the toxic pathway revealed in the present study may be primary and universal. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-022-00484-9.