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Identification of Urolithin A as a Metabolite Produced by Human Colon Microflora from Ellagic Acid and Related Compounds
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文摘
Dietary ellagic acid and related polyphenols are metabolized in humans to dibenzopyran-6-onederivatives, and the microbial origin of these metabolites has been suggested. However, this has notbeen demonstrated so far. Fecal samples donated by six volunteers were incubated under anaerobicconditions, and aliquots were used to evaluate the fecal metabolism of ellagic acid, the ellagitanninpunicalagin, and an ellagitannin rich extract from walnuts. The isoflavone daidzein was also incubatedwith the same fecal samples to follow the production of the microbial metabolites previously reported(dihydrogenistein, O-demethylangolensin, and equol) as a positive control of the system and toevaluate similarities between isoflavone and ellagic acid fecal flora metabolism. After fermentationthe metabolite "urolithin A" (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) was produced from ellagicacid, punicalagin, and the ellagitannin extract in all the fecal cultures from different volunteers, butwith very different production rates and concentrations. This large variability in the concentration ofmetabolite and kinetics of metabolite production is consistent with the large variability found in theexcretion of these metabolites in urine in vivo after human consumption of ellagitannins, and withdifferences in the composition of the fecal microflora. No correlation between isoflavone and ellagicacid metabolism by fecal microflora was observed. The present study confirms the microbial originof the recently reported in vivo generated hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives in humansand is a further step in the study of the bioavailability and metabolism of ellagic acid and ellagitannins.Keywords: Ellagitannin; ellagic acid; polyphenol; metabolism; colonic microflora; dihydroxy-6H-dibenzo[b,d]pyran-6-one; urolithin A; walnut; pomegranate; punicalagin

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