mTOR-Mediated Autophagy Regulates Fumonisin B1-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

Fumonisin B₁ (FB₁) is a fungal metabolite, which has an incremental detection rate in grains and feed worldwide. The nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is a critical element in pyroptosis activation, which participates in regulating enteritis. Meanwhile, autophagy is also engaged in intestinal inflammation. However, the function of pyroptosis and autophagy in FB₁-mediated enterotoxicity remains unclear. In this study, we explored the effects of FB₁ on enteritis and the underlying mechanism in vivo and in vitro. Our data showed that FB₁ exposure damaged the intestinal epithelium and promoted the secretion of inflammatory cytokines. Meanwhile, FB₁ exposure significantly upregulated the expression of pyroptosis-related genes. Then, MCC950, an inhibitor of NLRP3, significantly blocked FB₁-induced pyroptosis in IPEC-J2 cells. In addition, FB₁ treatment elevated the levels of autophagy. Moreover, the phosphorylation of the mammalian target of rapamycin (mTOR), an upstream protein of the autophagy pathway, was inhibited by FB₁ exposure. Notably, rapamycin, an inhibitor of mTOR, instead of MHY1485, an agonist of mTOR, could ameliorate FB₁-induced intestinal inflammatory injury and inhibit the upregulation of pyroptosis-related genes. In summary, we demonstrated that autophagy exhibited a protective effect against NLRP3 inflammasome-dependent pyroptosis on FB₁-induced enteritis. Our data clarify a favorable protective role for the activation of autophagy in FB₁ poisoning.