Microplastics (MPs) and
tributyltin (TBT) are both potential
environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both
pollutants) on mammals remain unclear. In this study, Ф5μm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced
inflammation in the liver, altered gut microbiota composition and disturbed fecal
bile acids profiles. In addition to decreasing
triglyceride (TG) and increasing
aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic
cholestasis by stimulating the expression of the
cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting
multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and
bile-salt export pump (BSEP) to prevent
bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased
7-ketolithocholic acid (7-ketoLCA) and
taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased
interferon γ (IFNγ) and Mpeg1 levels to induce
inflammation, accompanied by decreased 7-ketoLCA,
tauro-alpha-muricholic acid (T-alpha-MCA) and
alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced
bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome
dysbiosis and subsequently alter
bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.