Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the bi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Nutrition |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.912591/full |
| _version_ | 1818207996653600768 |
|---|---|
| author | Fang Li Yanhui Han Xian Wu Xiaoqiong Cao Zili Gao Yue Sun Minqi Wang Hang Xiao |
| author_facet | Fang Li Yanhui Han Xian Wu Xiaoqiong Cao Zili Gao Yue Sun Minqi Wang Hang Xiao |
| author_sort | Fang Li |
| collection | DOAJ |
| description | Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo. |
| first_indexed | 2024-12-12T04:37:48Z |
| format | Article |
| id | doaj.art-32673b8319394f2aa42c7ec0fe2c66d3 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-12-12T04:37:48Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-32673b8319394f2aa42c7ec0fe2c66d32022-12-22T00:37:55ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-05-01910.3389/fnut.2022.912591912591Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of ResveratrolFang Li0Yanhui Han1Xian Wu2Xiaoqiong Cao3Zili Gao4Yue Sun5Minqi Wang6Hang Xiao7Department of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesDepartment of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesDepartment of Kinesiology and Health, Miami University, Oxford, OH, United StatesDepartment of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesDepartment of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesDepartment of Tea and Food Science, Anhui Agricultural University, Hefei, ChinaDepartment of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesDepartment of Food Science, University of Massachusetts-Amherst, Amherst, MA, United StatesAlthough resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.https://www.frontiersin.org/articles/10.3389/fnut.2022.912591/fullresveratrolbiotransformationmetabolitesgut microbiotabiological activities |
| spellingShingle | Fang Li Yanhui Han Xian Wu Xiaoqiong Cao Zili Gao Yue Sun Minqi Wang Hang Xiao Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol Frontiers in Nutrition resveratrol biotransformation metabolites gut microbiota biological activities |
| title | Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol |
| title_full | Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol |
| title_fullStr | Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol |
| title_full_unstemmed | Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol |
| title_short | Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol |
| title_sort | gut microbiota derived resveratrol metabolites dihydroresveratrol and lunularin significantly contribute to the biological activities of resveratrol |
| topic | resveratrol biotransformation metabolites gut microbiota biological activities |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.912591/full |
| work_keys_str_mv | AT fangli gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT yanhuihan gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT xianwu gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT xiaoqiongcao gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT ziligao gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT yuesun gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT minqiwang gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol AT hangxiao gutmicrobiotaderivedresveratrolmetabolitesdihydroresveratrolandlunularinsignificantlycontributetothebiologicalactivitiesofresveratrol |