Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds
Abstract
Dietary ellagic acid and related polyphenols are metabolized in humans to dibenzopyran-6-one derivatives, and the microbial origin of these metabolites has been suggested. However, this has not been demonstrated so far. Fecal samples donated by six volunteers were incubated under anaerobic conditions, and aliquots were used to evaluate the fecal metabolism of ellagic acid, the ellagitannin punicalagin, and an ellagitannin rich extract from walnuts. The isoflavone daidzein was also incubated with 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 to evaluate similarities between isoflavone and ellagic acid fecal flora metabolism. After fermentation the metabolite "urolithin A" (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) was produced from ellagic acid, punicalagin, and the ellagitannin extract in all the fecal cultures from different volunteers, but with very different production rates and concentrations. This large variability in the concentration of metabolite and kinetics of metabolite production is consistent with the large variability found in the excretion of these metabolites in urine in vivo after human consumption of ellagitannins, and with differences in the composition of the fecal microflora. No correlation between isoflavone and ellagic acid metabolism by fecal microflora was observed. The present study confirms the microbial origin of the recently reported in vivo generated hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives in humans and is a further step in the study of the bioavailability and metabolism of ellagic acid and ellagitannins.
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The health benefits of consumption of pomegranate and pomegranate juice are attributed to the activities of urolithins.
“The health benefits of consumption of pomegranate and pomegranate juice are attributed to the activities of these urolithins.130,131”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [131]
UroA can only be detected in ∼40%-50% of human subjects upon consumption of EA/ET-containing diets.
“However, UroA can only be detected in ∼ 40%–50% of human subjects upon consumption of EA/ET-containing diets.131,136, 137, 138, 139, 140, 141, 142, 143”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [131]
There is substantial interindividual variability in the rate and concentration of urolithin A following consumption of pomegranate-derived polyphenols ellagic acid, punicalagin, and ellagitannin.
“For example, there is substantial interindividual variability in the rate and concentration of the bioactive metabolite urolithin A following consumption of the pomegranatederived polyphenols ellagic acid, punicalagin, and ellagitannin (508).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [508]
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- Authors
- Cerdá, B., Periago, P., Espín, J. C., & Tomás-Barberán, F. A.
- Affiliations
- Centro de Edafología y Biología Aplicada del Segura (ES)
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus Universitario de Espinardo, Murcia, Spain
- Venue
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-06-17
- Volume
- 53
- Issue
- 14
- Pages
- 5571-5576
- ISSN
- 0021-8561 (ISSN-L)
- 1520-5118
- OpenAlex
- W2047475718
- Cited by
- 301
- References
- 15
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 20 · 2023: 14 · 2022: 31 · 2021: 25 · 2020: 30 · 2019: 21 · 2018: 12 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 9 · 2013: 21 · 2012: 13
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Agricultural and Food Chemistry (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- urolithin A, ellagic acid, ellagitannins, punicalagin, Juglans regia, gut microbiota, fecal fermentation, microbial metabolism, daidzein, isoflavone metabolism, equol, bioavailability, polyphenol metabolism
- MeSH terms
- Bacteria, Colon, Coumarins, Diet, Ellagic Acid, Feces, Fermentation, Flavonoids, Humans, Isoflavones, Phenols, Hydrolyzable Tannins, Polyphenols
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