Ingestion of Poly-Ethylene Terephthalate Nanofragments Derived from Plastic Bottles Triggers Long-term Gut Inflammation and Microbiome Dysbiosis in Mice

Despite extensive research on polystyrene (PS) nanoplastics (NPs), the gastrointestinal health effects of representative NPs used in food and beverage packaging, for instance, polyethylene terephthalate (PET) used in water bottles, remain underexplored. Addressing this gap, female C57BL/6 mice were here exposed to PET (30–500 nm) and PS (50 nm and 200 nm) NPs via gavage to assess the histological, immunological, genotoxic, and microbiome alterations at days 1, 7 and 28 after exposure (single dose: 20 mg/kg bw). We found that PET NPs showed the most pronounced effects, including early liver DNA damage, chronic colonic inflammation, and downregulation of cell cycle and repair genes. Moreover, 16S rRNA gene sequencing revealed that PET exposure led to both a reduction in gut microbial diversity and beneficial taxa ( Odoribactera and Anaerotruncus ) and an increase in inflammatory taxa ( Roseburia and Neglecta ), demonstrating that the unresolved gut inflammation was closely linked to gut dysbiosis. Conversely, PS200 caused transient jejunal DNA damage while PS50 led to both prolonged liver genotoxicity and lymphocyte depletion in mesenteric lymph nodes. Overall, all NPs triggered distinct structural and inflammatory changes in the gut, but PET NPs’ disturbances, often seen in inflammatory diseases such as inflammatory bowel disease, were the greatest. Our findings highlight that ingestion of PET NPs poses risks for gut health and microbial homeostasis, underscoring the need for further investigation into their impact after chronic ingestion. This work also suggests that greater regulatory attention should be paid to these ubiquitous contaminants of the daily human diet and key indicator of the exposome.