Sustained oral intake of nano-iron oxide perturbs the gut-liver axis

Nanomaterial have shown excellent properties in the food industry. Although iron oxides are often considered safe and widely used as food additives, the toxicity of nano-iron oxide remains unclear. Here we established a subchronic exposure mouse model by gavage, tested the biodistribution of nano-iron oxide, and explored the mechanism of liver injury caused by it through disturbance of the gut-liver axis. Oral intake of nano-iron oxide will likely disrupt the small intestinal epithelial barrier, induce hepatic lipid metabolism disorders through the gut-liver axis, and cause hepatic damage accompanied with hepatic iron deposition. Nano-iron oxide mainly caused hepatic lipid metabolism disorder by perturbing glycerophospholipid metabolism and the sphingolipid metabolism pathways, with the total abundance of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) tending to decrease while that of triglyceride tended to increase, in a time-and dose-dependent manner. The imbalanced lipid homeostasis could cause damage via membrane disruption, lipid accumulation, and lip-otoxicity. This data provides information about the subchronic toxicity of nano-iron oxide, highlights the importance of gut-liver axis in the hepatotoxicity.

Automated summary

We established a subchronic exposure mouse model to investigate the toxicity of nano-iron oxide in the food industry. The results showed that oral intake of nano-iron oxide can disrupt the small intestinal epithelial barrier, induce hepatic lipid metabolism disorders through the gut-liver axis, and cause hepatic damage accompanied with hepatic iron deposition. This study highlights the importance of the gut-liver axis in the hepatotoxicity of nano-iron oxide.