Deoxynivalenol triggers porcine intestinal tight junction disorder through hijacking SLC5A1 and PGC1α-mediated mitochondrial function.

Deoxynivalenol (DON) is a mycotoxin frequently occurring in human and animal food worldwide, which raises increasing public health concerns. Growing evidence suggests that mitochondria is a pivotal molecular target for DON. However, the contribution of mitochondrial dysfunction to the pathogenesis of DON-induced gut epithelial barrier disruption remains poorly understood. In an animal experiment, piglets exposed to 2.89 mg DON/kg feed for 4 weeks showed altered metabolomic profiling in the serum and compromised transcriptome in the jejunum. DON exposure also impaired mitochondrial structure in the jejunal mucosa, corresponding with dysfunction of the tight junctions. In IPEC-J2 cells, metabolomic and transcriptomic analyses revealed that DON exposure perturbed biological processes occurring in the mitochondria and disordered the expression of genes involved in mitochondrial energy metabolism. Fuel utilization from glucose was affected by DON exposure, as were mitochondrial morphological dynamics leading to increased fragmentation. A marked loss of Na+/glucose cotransporter (SLC5A1) and peroxisome proliferator activated receptor-γ co-activator 1α (PGC1α) was observed in DON-treated cells. Taken together, our data highlight the critical role of impaired mitochondrial energy metabolism and mitochondrial biogenesis in abnormal intestinal tight junction upon DON exposure, and provide a potential mitochondrial target for intestinal mucosal restoration following DON exposure.