Polystyrene nanoplastics readily penetrate intestine and cause sex-specific effects mediated by bile acids and microbiome

Orally ingested nanoplastics can enter the blood flow; however, their digestive tract fate is unclear. We found that ∼60% of ingested polystyrene nanoparticles (PSNPs) cross the intestine wall in 3 h, but most are captured by the liver and discharged via the biliary system. Nanoparticle-bound bile acids (BAs) and apical sodium-dependent bile acid transporter (ASBT) mediate this fast absorption of PSNPs. In the liver, PSNPs block CYP7A1 degradation by disrupting lysosome biogenesis, which promotes BA synthesis and increases colitis susceptibility of mice by reducing Lactobacillus and increasing Enterobacteriaceae. Significant sexual dimorphism is unexpectedly discovered after PSNP treatment, where male mice are more sensitive than females due to the higher ASBT expression on enterocytes in males. In summary, our results could guide usage of plastic and prompt design of efficient carriers for oral drug delivery as well as indicate that sex should not be ignored both in drug administration and disease.