Polystyrene microplastics and hepatic fibrosis-related indices in type 2 diabetes: a cross-sectional analysis with...

Microplastics (MPs) are emerging environmental contaminants with potential hepatotoxicity, yet direct epidemiological evidence linking internal MP exposure to liver injury is scarce, particularly in individuals with type 2 diabetes (T2D). In this cross-sectional study nested within the METAL2 cohort, we aimed to characterize blood microplastic profiles in patients with T2D and to determine whether specific MP polymers are associated with hepatic steatosis and fibrosis risk, with experimental validation of the identified polymer.

In patients with T2D, multiple MP polymers were detectable in blood, with polyvinyl chloride (PVC), polyamide 66 (PA66), and polystyrene (PS) being the most prevalent. Although PVC constituted the largest proportion of total MP burden, PS showed the most consistent nominal positive liver-related signal in the human analyses, including higher levels in participants with elevated fibrosis risk and higher FIB-4 and ALT in the highest exposure quartile. Experimental validation in diabetic mice demonstrated that PS microplastics markedly exacerbated hepatic steatosis, inflammation, and collagen deposition, leading to overt liver fibrosis. Mechanistically, PS-MPs exposure disrupted hepatic lipid homeostasis and concurrently activated the NLRP3 inflammasome and the TGF-β1/Smad signaling pathway, promoting inflammatory amplification and hepatic stellate cell activation.

This integrated human and experimental study provides preliminary evidence that circulating PS-associated signals are linked to liver-related indices in T2D, while experimental findings support the biological plausibility that PS exposure may aggravate hepatic injury under diabetic conditions.