Co-exposure to boscalid and TiO (E171) or SiO (E551) downregulates cell junction gene expression in small intestinal epithelium cellular model and increases pesticide translocation.

A recent published study showed that TiO (E171) and SiO (E551), two widely used nano-enabled food additives, increased the translocation of the commonly used pesticide boscalid by 20% and 30% respectively. Such increased absorption of pesticides due to the presence of engineered nanomaterials (ENMs) in food raises health concerns for these food additives. In this companion study, mRNA expression of genes related to cell junctions in a small intestinal epithelial cellular model after exposure to simulated digestas of fasting food model (phosphate buffer) containing boscalid (150 ppm) with or without either TiO or SiO (1% w/w) were analyzed. Specific changes in cell barrier function underlying or contributing to the increased translocation of boscalid observed in the previous study were assessed. Results showed that exposure to boscalid alone has no significant effect on cell junction genes, however, co-exposure to boscalid and TiO significantly regulated expression of cell-matrix junction focal adhesion-related genes, e.g., downregulating Cav1 (-1.39-fold, p < 0.05), upregulating Cav3 (+ 3.30-fold, p < 0.01) and Itga4 (+ 3.30-fold, p < 0.05). Similarly, co-exposure to boscalid and SiO significantly downregulated multiple cell-cell junction genes, including tight junction genes (Cldn1, Cldn11, Cldn16, Cldn18, and Jam3), adherens junction genes (Notch1, Notch3, Pvrl1) and gap junction genes (Gja3 and Gjb2), as well as cell-matrix junction focal adhesion genes (Itga4, Itga6, Itga7). Together, these findings suggest that co-ingestion of boscalid with TiO (E171) or SiO (E551) could cause weakening of cell junctions and intercellular adhesion, which could result in dysregulation of paracellular transport, and presumably contributed to the previously observed increased translocation of boscalid at the presence of these ENMs. This novel finding raises health safety concerns for such popular food additives.