Dietary components regulate the gastrointestinal fate of polystyrene nanoplastics through differential aggregation, mucus transport and Caco-2 cell interactions.

Micro(nano)plastics (MNPs) behaviour in the gastrointestinal (GI) tract is modulated by co-ingested food components, yet these effects remain poorly quantified. This study aimed to investigate how ghee, casein, and cellulose influence the transformation and cellular interactions of 200 nm polystyrene (PS) under simulated GI digestion. Changes in PS aggregation were evaluated in stomach and small intestinal digesta by the flow cytometer. The potential mucus penetration capacity of digested PS particles was further assessed through the spinning disk confocal microscopy, while mitochondrial activity and cellular interaction were examined using Caco-2 cells. The results showed that upon in vitro digestion, casein reduced PS aggregation, while cellulose and ghee promoted PS aggregation. The percentage of cells interacting with PS in cellulose, casein and ghee small intestinal digesta were 18.4% ± 3.1%, 36.0% ± 5.2% and 34.6% ± 7.8%, respectively. These results demonstrate that dietary composition influenced MP physicochemical evolution and downstream biological interactions.