Metabolomic profiling reveals intestinal toxicity in zebrafish upon single and combined exposure to polystyrene...

Polystyrene microplastics (PS-MPs) and azithromycin (AZM) are widely detected in aquatic environments, yet the mechanisms underlying their combined toxicity remain unclear. In this study, zebrafish were employed as a model organism to investigate the toxic effects of single and combined exposure to PS-MPs and AZM on intestinal health of zebrafish. Results demonstrated that the accumulation of PS-MPs in zebrafish intestines exhibited size-dependent characteristics-smaller particle sizes led to higher accumulation levels. Histopathological analysis revealed that single exposure to either PS-MPs or AZM induced intestinal structural damage. Notably, combined exposure at medium and high concentrations caused more severe damage compared to the AZM-only groups. The specific manifestations included reduced villus height, decreased goblet cell count, aggravated vacuolization, and loss of striated border. Analysis of oxidative stress indicated that PS-MPs exacerbated AZM-induced oxidative damage, intensifying intestinal oxidative stress. Additionally, the alteration of intestinal lipopolysaccharide levels reflected the modulation of gut barrier integrity and inflammatory response under combined exposure. Metabolomic analysis showed that the significantly altered metabolites induced by combined exposure to PS-MPs and AZM were mainly involved in metabolic pathways such as arginine biosynthesis, sphingolipid metabolism, purine metabolism, alanine-aspartate-glutamate metabolism, and pantothenate and CoA biosynthesis. This suggests that combined exposure significantly disrupts the metabolic homeostasis of zebrafish. This study provides key mechanistic evidence for assessing the ecological risks of combined PS-MPs and AZM pollution, reveals the interaction between oxidative stress and metabolic disturbance, clarifies the mechanism of their combined toxicity, and offers metabolomic support for evaluating the ecological risks of the synergistic effects of MPs and antibiotics.