Comparative Analysis of Metabolic Dysfunctions Associated with Pristine and Aged Polyethylene Microplastic Exposure via the Liver-Gut Axis in Mice

The accumulation of plastic waste in the environment has raised widespread concern about the impact of microplastics (MPs) on human and environmental health, particularly regarding aged MPs. This study investigated the effects of subchronic dietary intake on pristine and aged polyethylene microplastics (PE-MPs) in C57BL/6J mice. Results revealed that both pristine and aged PE-MPs, at doses of 0.01 and 1 mg/day, induced plasma metabolic changes primarily associated with lipid metabolism and digestive processes. These alterations were reflected in the expression changes of proteins involved in unsaturated fatty acid pathways in the liver as well as a reduction in beneficial gut microbiota. Key contributors in the toxicity of aged PE-MPs included ATP-binding cassette transporters, gut bacteria alterations (notably <i>Lactobacillus</i>, <i>Akkermansia</i>, <i>Parasutterella</i>, and <i>Turicibacter</i>), and significantly altered proteins related to fatty acid elongation, such as acyl-CoA thioesterase enzyme family and elongation of very long chain fatty acid protein 5. These disruptions exacerbated lipid metabolism disorders, potentially contributing to metabolic diseases. Additionally, decreased levels of glutathione S-transferase A proteins, along with reduced hepatic glutathione and increased reactive oxygen species in both the small intestine and liver, suggested that aged PE-MPs aggravated hepatic and intestinal damage through oxidative stress. These findings indicated that aged PE-MPs caused more severe hepatic dysfunction and gut microbiota disruption. This effect was likely mediated by the transfer of fatty acids and signaling molecules through the gut-liver axis, ultimately leading to hepatic lipid metabolism disorders and oxidative stress.