Chronic PET-Microplastic Exposure: Disruption of Gut-Liver Homeostasis and Risk of Hepatic Steatosis.

Microplastics (MPs) are pervasive pollutants found in environments and food, with humans experiencing continuous exposure. Polyethylene terephthalate (PET) is a major plastic contaminant detected in food and beverages. However, the chronic effects of environmentally relevant, physically abraded PET-MPs on health, on the liver, remain elusive. This study investigates the hepatotoxicity of the PET-MPs following long-term exposure, with a focus on the gut-liver axis interactions and transcriptomic responses. Male mice are exposed to PET-MPs (5 mg week-1) from 5 to 34 weeks of age. Environmentally mimetic PET particles are prepared by grinding plastic bottles. Prolonged exposure to MPs for 29 weeks led to increased adiposity and obesity. The mice exposed to PET-MPs developed hepatomegaly, steatosis, and early-stage fibrosis. Transcriptome data revealed the downregulation of genes involved in mitochondrial energy metabolism and the upregulation of lipid droplet and fibrotic pathway genes. Gut microbiota is also significantly changed, with a decrease in Bacteroides and Lachnospiraceae, which maintain gut homeostasis. Disruption of bile acid metabolism and fecal color change further indicated impairment of the gut-liver axis. These findings provide new toxicological insights and emphasize the requirement to reassess the public health risks posed by long-term MPs ingestion.