Polystyrene Microplastics and Bisphenol A Exposure Worsen Intestinal Injury in Diabetic Mice by Disrupting Gut Microbiota and Metabolites

Environmental pollutants can induce multiorgan damage, with the digestive tract particularly susceptible. Diabetic enteropathy is a significant complication of type 2 diabetes mellitus (T2D). However, the relationship between environmental pollutant exposure and T2D-associated intestinal injury has not been previously explored. In this study, T2D mice were subjected to polystyrene microplastics (PS-MPs, 100 μg/day, 3 weeks) and bisphenol A (BPA, 100 μg/kg/day, 2 weeks). Metabolomics and 16S rRNA sequencing were used to detect changes in colonic metabolites and gut microbial composition. Caco-2 cells were utilized to investigate the functions of the altered metabolites. Compared to the T2D group, mice exposed to PS-MPs and BPA exhibited shorter colon length and reduced levels of gut barrier proteins ZO-1 and Occludin. Metabolomics analysis revealed that PS-MPs primarily affected colonic long-chain fatty acids (LCFAs) and adenosine metabolism, while BPA disrupted α-ketoisovaleric acid (KIVA) and pyruvic acid (PyrA) homeostasis. Moreover, PS-MPs exposure altered the abundance of Duncaniella and Olsenella, while BPA primarily affected Phocaeicola, Olsenella, and Variovorax. In vitro experiments showed that palmitoleic acid (C16:1), γ-linolenic acid (C18:3), adenosine (Ado), and KIVA promoted the expression of ZO-1 in Caco-2 cells. Our findings provide valuable insights into the impact of environmental pollutants on intestinal injury in T2D, underscoring the importance of environmental contaminant management, particularly in susceptible populations.