Distinct Effects between Polystyrene Micro- and Nanoplastics: Exacerbation of Adverse Outcomes in Inflammatory Bowel Disease-like Zebrafish and Mice

Numerous studies have demonstrated that micro- and nanoplastics can induce adverse effects in both zebrafish and mice, primarily targeting the intestine in oral exposure scenarios. Organisms under disease conditions are suggested to exhibit increased susceptibility to environmental pollutants, with inflammatory bowel disease (IBD) serving as a relevant model for understanding toxicity initiated in a diseased intestine. Here, we compared the adverse outcomes of polystyrene micro- (PSMPs) and nanoplastics (PSNPs) in both normal and IBD-like zebrafish and mouse models. We found that in zebrafish, no significant difference in mortality was elicited by the two particles, while IBD-like fish exhibited greater susceptibility to exposure. Conversely, transcriptomic analysis of surviving fish revealed that PSNPs disrupted metabolic pathways, particularly galactose metabolism, and induced more pronounced apoptosis in intestinal epithelial cells compared to PSMPs in IBD-like fish. These effects were further associated with an increase in the genus <i>Flavobacterium</i>. Similarly, in IBD-like mice, PSNPs induced a more significant increase in crypt length than control mice and more severe histological injury and greater disruptions in gut microbial diversity compared to PSMPs, mirroring the findings in zebrafish. Notably, two shared pathways, glycosphingolipid synthesis (globo and isoglobo series) and NOD-like receptor signaling, were identified in response to PSNP and PSMP exposure in two models, respectively, along with a consistent decline in Firmicutes abundance. These findings suggest that smaller-sized PSNPs may pose higher environmental and health risks compared to larger-sized PSMPs, providing key insights into the interactions between polystyrene particles and compromised biological systems and their resulting adverse outcomes.