The toxicological effects of perfluorooctanoic acid (PFOA) exposure in large yellow croaker (Larimichthys crocea): exploring the relationship between liver damage and gut microbiota dysbiosis

Abstract

Per- and polyfluoroalkyl substances (PFASs) are synthetic organofluorine compounds characterized by their persistence, toxicity, and bioaccumulative properties, rendering them substantial environmental contaminants. However, limited research has investigated the effects of a short-term low-concentration PFAS exposure on the hepatic and intestinal systems of marine fish. In this study, large yellow croaker was selected as the experimental subject to explore the toxic effects of exposure to 1000 ng/L PFOA after 3, 7, and 14 days, with a focus on liver and gut microbiota. The results demonstrated that a short-term exposure to PFOA induced significant histopathological damage in both liver and gut, with cumulative effects becoming more pronounced over time. Moreover, transcriptome analysis of the liver revealed that PFOA exposure significantly altered the expression of genes associated with lipid metabolism, inflammatory response, and cellular apoptosis. GO and KEGG functional enrichment analyses showed significant enrichment in the P53, NF-κB, MAPK, and PPAR signaling pathways. On the other hand, 16S rRNA gene sequencing demonstrated that PFOA exposure resulted in a decline in gut microbiota diversity, an increase in the abundance of potentially pathogenic bacteria (e.g. Proteobacteria), and a significant reduction in beneficial bacteria (Lactobacillus). These changes indicated gut microbiota dysbiosis. Correlation analysis between gut microbiota changes and potential liver damage indicators suggested an association between liver damage and gut microbiota dysbiosis. Furthermore, we propose a hypothetical model involving lipid accumulation-mediated mitochondrial oxidative stress and inflammation pathway activation, triggered by damage-associated molecular patterns (DAMPs) resulting from PFOA exposure. These findings offered valuable insights into the toxic effects of a short-term low-concentration PFOA on the hepatic and intestinal systems of large yellow croaker, and establish a connection between liver damage to gut microbiota dysbiosis after PFOA exposure.