Assessment of the adverse impacts of aflatoxin B on gut-microbiota dependent metabolism in F344 rats.

The adverse impacts of AFB on gut-microbiota dependent metabolism in F344 rats were assessed via ultra-high performance liquid chromatography (UHPLC)-profiling and UHPLC-mass spectrometry (MS) metabolomic analyses. UHPLC-profiling analysis found 1100 raw peaks from the fecal samples collected at week 4, of which 335 peaks showed peak shape qualified for quantitation. A total of 24, 40 and 71 peaks were significantly decreased (>2-fold, p < 0.05) among the exposure groups treated with 5, 25, and 75 μg AFB kg body weight (B. W.), respectively. Supervised orthogonal partial least squares projection to latent structures-discriminant analysis revealed 11 differential peaks that may be used to predict AFB-induced adverse changes of the metabolites. UHPLC-MS based metabolomic analysis discovered 494 features that were significantly altered by AFB, and 234 of them were imputatively identified using Human Metabolome Data Base (HMDB). Metabolite set enrichment analysis showed that the highly disrupted metabolic pathways were: protein biosynthesis, pantothenate and CoA biosynthesis, betaine metabolism, cysteine metabolism, and methionine metabolism. Eight features were rated as indicative metabolites for AFB exposure: 3-decanol, xanthylic acid, norspermidine, nervonyl carnitine, pantothenol, threitol, 2-hexanoyl carnitine, and 1-nitrohexane. These data suggest that AFB could significantly reduce the variety of nutrients in gut and disrupt a number of gut-microbiota dependent metabolic pathways, which may contribute to the AFB-associated stunted growth, liver diseases and the immune toxic effects that have been observed in animal models and human populations.