Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis
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.
Authors
- Tzu-Wen Cross (ORCID: https://orcid.org/0000-0002-8856-8578)
- Tyler K. Ulland
- Federico E. Rey (ORCID: https://orcid.org/0000-0002-0239-7780)
- Rubén Aquino-Martínez (ORCID: https://orcid.org/0000-0003-1564-2279)
- Kazuyuki Kasahara (ORCID: https://orcid.org/0000-0003-3303-7216)
- Fredrik Bäckhed (ORCID: https://orcid.org/0000-0002-4871-8818)
- Colin D. Kay (ORCID: https://orcid.org/0000-0001-7290-4496)
- Bradley W. Bolling (ORCID: https://orcid.org/0000-0002-4222-2467)
- Jessica Everhart
- Abigail H. Evered
- Robert L. Kerby (ORCID: https://orcid.org/0000-0003-1565-6486)
Institutions
- University of Wisconsin System (US)
- University of Wisconsin–Madison (US)
- North Carolina State University (US)
- Nanyang Technological University (SG)
- Purdue University West Lafayette (US)
- Sahlgrenska University Hospital (SE)
- Region Västra Götaland (SE)
- David H. Murdock Research Institute (US)
- University of Gothenburg (SE)
Publication Details
- Journal
- npj Biofilms and Microbiomes
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1038/s41522-024-00626-1
- Citations
- 21
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 16.93
Funders
- University of Wisconsin-Madison
- Ministry of Education - Singapore
- Nanyang Technological University
- Fondation Leducq
- National Institutes of Health
- Medical Research Council
- National Medical Research Council
- Lee Kong Chian School of Medicine, Nanyang Technological University
- National Heart, Lung, and Blood Institute