Aflatoxin B1 Disrupts Gut-Microbial Metabolisms of Short-Chain Fatty Acids, Long-Chain Fatty Acids, and Bile Acids in Male F344 Rats.

Abstract

In this study, male F344 rats were orally exposed to aflatoxin B1 (AFB1) at 0, 5, 25, and 75 μg/kg for 4 weeks. Rat feces were collected from 2 to 4 weeks following exposure and were assessed for gut-microbiota-dependent metabolites. Gut-microbiota-related organic acids were quantitated in the feces using 2-nitrophenylhydrazine derivatization coupled HPLC-profiling method which was validated and showed good reliability, accuracy and sensitivity. After 2-week exposure, AFB1 significantly reduced the levels of fecal short-chain fatty acids (SCFAs) with an over 70% reduction in the high-dose group (75 μg/kg). Mixed-effects model revealed an inverse correlation between AFB1 dose and fecal levels of SCFAs, but no significant time effect was found. When compared with the control, oral exposure to middle-dose AFB1 (25 μg/kg) resulted in remarkable elevations of fecal cholic acid (2.18-fold), linoleic acid (cis-9, cis-12-18:2) (11.3-fold), pentadecanoic acid (15: 0) (3.68-fold), pyruvic acid (4.56-fold), and 3-phenyllactic acid (3.74-fold), but deoxycholic acid level was reduced by 41% in the low-dose group (5 μg/kg). These results demonstrated the disruptions of several important gut-microbiota metabolic pathways, including the synthesis of SCFAs, pyruvic acid related pathways, metabolisms of amino acids, bile acids and long-chain fatty acids, which may further affect host digestive efficiency, energy supply, intestinal immunity, production of neurotransmitters, and enterohepatic cross-talk. Our study suggests that the impairment of gut-microbiota-dependent metabolism may contribute to pathological mechanisms of AFB1-induced adverse health effects.