Differential effects of foodborne and waterborne micro(nano)plastics exposure on fish liver metabolism and gut microbiota community

Micro(nano)plastics (MNPs) primarily enter fish through two routes: directly ingestion via their diets and respiratory filtration through their gills. However, the specific impacts of these two routes on liver metabolism remain largely unknown. Here, we investigated the gene expression profiles of the liver of Nile tilapia Oreochromis niloticus following equivalent doses of foodborne and waterborne MNPs exposure. While the liver phenotypes of O. niloticus showed minimal differences between the two exposure routes, significant variations were observed in gene response patterns. Using WGCNA, we identified the key gene networks and KEGG pathways associated with each exposure type. The primary transcription factors regulating gene expression changes were thrb for foodborne exposure and fosl2 for waterborne exposure. The stimulus of foodborne MNPs primarily induced metabolic disorders through circadian rhythm, whereas waterborne MNPs induced inflammatory responses to affect host metabolism. By integrating gene expression alterations with gut microbiota enrichment data, we further found that Firmicutes, Fusobacteriota, Proteobacteria, and Chloroflexi jointly regulated the expression of mapk13 during foodborne exposure, whereas the expression of the most leading genes in waterborne exposure was predominantly influenced by Firmicutes. Collectively, our study demonstrated a distinct pattern in microbiota-gene gut-liver axis in O. niloticus in response to foodborne and waterborne MNPs exposure. © 2025 The Authors