Fumonisin B induced intestinal epithelial barrier damage through endoplasmic reticulum stress triggered by the ceramide synthase 2 depletion.

Fumonisin B (FB) contamination in feed is of great concern nowadays. The intestine would be the first line when FB-contaminated food or feed was ingested. However, the intestinal toxicity and mechanism of FB have rarely been studied. In this study, we found that FB inhibited cell viability, and promoted the severe release of lactate dehydrogenase. Meantime, FB destroyed the intestinal physical barrier by reducing the expressions of tight junctions. And FB induced excessive production of cytokines like tumor necrosis factor-α, resulting in damage to the intestinal immunological barrier. Furthermore, we observed that FB preferentially inhibited the expressions of ceramide synthase 2 (CerS2) and upregulated the expression of endoplasmic reticulum (ER) stress markers. The siRNA-mediated knockdown of CerS2 and CerS2 overexpression proved that CerS2 depletion induced by FB triggered ER stress, which then destructed the intestinal barrier. FB-induced intestinal impairment could be restored by CerS2 over-expression or 4-Phenylbutyric acid (ER stress inhibitor). Overall, our findings demonstrated intestinal toxicity and potential mechanism of FB, and the intestinal impairment risk posed by FB must be taken seriously.