The role of intestinal microflora in the metabolism of trichothecene mycotoxins.

ABSTRACT

The role of faecal and intestinal microflora on the metabolism of trichothecene mycotoxins was examined in this study. Suspensions of microflora obtained from the faeces of horses, cattle, dogs, rats, swine and chickens were incubated anaerobically with the trichothecene mycotoxin, diacetoxyscirpenol (DAS). Micro-organisms from rats, cattle and swine completely biotransformed DAS, primarily to the deacylated deepoxidation products, deepoxy monoacetoxyscirpenol (DE MAS) and deepoxy scirpentriol (DE SCP). By contrast, faecal microflora from chickens, horses and dogs failed to reduce the epoxide group in DAS and yielded only the deacylation products, monoacetoxyscirpenol (MAS) and scirpentriol (SCP), in addition to unmetabolized parent compound. Intestinal microflora obtained from rats completely biotransformed DAS to DE MAS, DE SCP and SCP; and T-2 toxin to the deepoxy products, deepoxy HT-2 (DE HT-2) and deepoxy T-2 triol (DE TRIOL). Rat intestinal microflora also biotransformed the polar trichothecenes, T-2 tetraol and scirpentriol, to their corresponding deepoxy analogues. Deepoxy T-2 toxin (DE T-2) was synthesized from T-2 toxin and demonstrated to be 400 times less toxic than T-2 toxin in the rat skin irritation bioassay and non-toxic to mice given 60 mg/kg ip, demonstrating that epoxide reduction is a significant single step detoxification reaction for trichothecene mycotoxins.