The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlateswith its inability to alter the metabolism of sphingolipids

Fumonisins are mycotoxins frequently found as natural contaminants in maize, where they are producedby the plant pathogen Fusarium verticillioides. They are toxic to animals and exert their effects throughmechanisms involving disruption of sphingolipid metabolism. Fumonisin B1 (FB1) is the predominantfumonisin in this family. FB1 is converted to its hydrolyzed analogs HFB1, by alkaline cooking(nixtamalization) or through enzymatic degradation. The toxicity of HFB1 is poorly documented especiallyat the intestinal level. The objectives of this study were to compare the toxicity of HFB1 and FB1 and to assessthe ability of these toxins to disrupt sphingolipids biosynthesis. HFB1 was obtained by a deesterification ofFB1 with a carboxylesterase. Piglets, animals highly sensitive to FB1, were exposed by gavage for 2 weeks to2.8 mmol FB1 or HFB1/kg body weight/day. FB1 induced hepatotoxicity as indicated by the lesion score, thelevel of several biochemical analytes and the expression of inflammatory cytokines. Similarly, FB1 impairedthe morphology of the different segments of the small intestine, reduced villi height and modified intestinalcytokine expression. By contrast, HFB1 did not trigger hepatotoxicity, did not impair intestinal morphologyand slightly modified the intestinal immune response. This low toxicity of HFB1 correlates with a weakalteration of the sphinganine/sphingosine ratio in the liver and in the plasma. Taken together, these datademonstrate that HFB1 does not cause intestinal or hepatic toxicity in the sensitive pig model and onlyslightly disrupts sphingolipids metabolism. This finding suggests that conversion to HFB1 could be a goodstrategy to reduce FB1 exposure.