| Abstract
| - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a putative human carcinogenic heterocyclicaromatic amine formed from meat and fish during cooking. Although the formation of hazardousPhIP metabolites by mammalian enzymes is well-documented, nothing is known about the PhIPtransformation potency of human intestinal bacteria. In this study, the in vitro metabolism of PhIP byhuman fecal samples was investigated. Following anaerobic incubation of PhIP with stools freshlycollected from six healthy volunteers, we found that PhIP was extensively transformed by the humanintestinal bacteria. HPLC analysis showed that the six human fecal microbiota transformed PhIPwith efficiencies from 47 to 95% after 72 h incubation, resulting in one major derivative. ESI-MS/MS,HRMS, 1D (1H, 13C, DEPT) and 2D (gCOSY, gTOCSY, gHMBC, gHSQC) NMR, and IC analysiselucidated the complete chemical identity of the microbial PhIP metabolite as 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3‘,2‘:4,5]imidazo[1,2-a]pyrimidin-5-ium chloride. At present, noinformation is available about the biological activity of this newly discovered bacterial PhIP metabolite.Our findings however suggest that bacteria derived from the human intestine play a key role in theactivation or detoxification of PhIP, a digestive fate ignored so far in risk assessments. Moreover,the variation in transformation efficiency between the human microbiota indicates interindividualdifferences in the ability to convert PhIP. This may predict individual susceptibility to carcinogenicrisk from this suspected dietary carcinogen. Keywords: heterocyclic amine; meat; cooking; intestinal bacteria; HPLC; LC-MS; NMR
|
