Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis
Abstract Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-024-00626-1 |
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| author | Kazuyuki Kasahara Robert L. Kerby Ruben Aquino-Martinez Abigail H. Evered Tzu-Wen L. Cross Jessica Everhart Tyler K. Ulland Colin D. Kay Bradley W. Bolling Fredrik Bäckhed Federico E. Rey |
| author_facet | Kazuyuki Kasahara Robert L. Kerby Ruben Aquino-Martinez Abigail H. Evered Tzu-Wen L. Cross Jessica Everhart Tyler K. Ulland Colin D. Kay Bradley W. Bolling Fredrik Bäckhed Federico E. Rey |
| author_sort | Kazuyuki Kasahara |
| collection | DOAJ |
| description | Abstract Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid. |
| format | Article |
| id | doaj-art-4871c35c04054e4084b264403d15187f |
| institution | Kabale University |
| issn | 2055-5008 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj-art-4871c35c04054e4084b264403d15187f2025-01-12T12:10:01ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-01-0111111010.1038/s41522-024-00626-1Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosisKazuyuki Kasahara0Robert L. Kerby1Ruben Aquino-Martinez2Abigail H. Evered3Tzu-Wen L. Cross4Jessica Everhart5Tyler K. Ulland6Colin D. Kay7Bradley W. Bolling8Fredrik Bäckhed9Federico E. Rey10Department of Bacteriology, University of Wisconsin-MadisonDepartment of Bacteriology, University of Wisconsin-MadisonDepartment of Bacteriology, University of Wisconsin-MadisonDepartment of Pathology and Laboratory Medicine, University of Wisconsin-MadisonDepartment of Bacteriology, University of Wisconsin-MadisonPlants for Human Health Institute, North Carolina State UniversityDepartment of Pathology and Laboratory Medicine, University of Wisconsin-MadisonPlants for Human Health Institute, North Carolina State UniversityDepartment of Food Science, University of Wisconsin-MadisonWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of GothenburgDepartment of Bacteriology, University of Wisconsin-MadisonAbstract Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid.https://doi.org/10.1038/s41522-024-00626-1 |
| spellingShingle | Kazuyuki Kasahara Robert L. Kerby Ruben Aquino-Martinez Abigail H. Evered Tzu-Wen L. Cross Jessica Everhart Tyler K. Ulland Colin D. Kay Bradley W. Bolling Fredrik Bäckhed Federico E. Rey Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis npj Biofilms and Microbiomes |
| title | Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| title_full | Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| title_fullStr | Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| title_full_unstemmed | Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| title_short | Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| title_sort | gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis |
| url | https://doi.org/10.1038/s41522-024-00626-1 |
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