The in vitro modulation of intestinal growth and inflammatory Indices by Fumonisin B1 and hydrolyzed Fumonisin B1 through protein network analyses

The intestinal epithelium is regularly exposed to contaminants like fumonisin mycotoxins which are associated with mycotoxicosis in various mammalian species. Fumonisin B₁ (FB₁) can also enzymatically convert to hydrolyzed fumonisin B₁ (HFB₁), a less potent ceramide synthase inhibitor, with contradictory outcomes in diverse <i>in vitro</i> and <i>in vivo</i> models. In this study, we evaluated the impact of FB₁ and HFB₁ on cell viability, apoptosis, and proliferation in the porcine intestinal cell line (IPEC-J2), while also monitoring inflammatory responses through interleukin 8 (IL-8) immune-detection. The molecular mechanisms and pathways influenced by FB₁ and HFB₁ exposure were further investigated through proteomic and bioinformatic analyses. Using Gene Ontology (GO), Differentially Abundant Proteins (DAPs) were identified and visualized by comparing <i>Homo sapiens</i> and porcine databases and 52 significant DAPs were found between FB₁ and HFB₁ in comparison to the control. Fibronectin 1 (FN1), an adhesive glycoprotein of the intestine, was consistently detected in cells exposed to FB₁ and HFB₁. FB₁ up-regulates FN1, while HFB₁ down-regulates it, leading to distinct cancer-promoting pathways as revealed by Cytoscape and STRING enrichment analysis. These results suggest that HFB₁ promotes a greater <i>in vitro</i> toxicity upon the IPEC-J2 cell line compared to FB₁, due to the abundance of proteins that were affected during exposure and the interconnectedness of pathways that were enriched.