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Flavonoids and polyphenols, which are abundant in colourful fruits and vegetables, have emerged as promising bioactive compounds for mitigating CVD. This study elucidates the mechanisms by which flavonoids exert cardioprotective effects through their antioxidant, prebiotic, and mitochondrial restorative properties. Flavonoids function as hydrogen donors, scavenging free radicals such as nitric oxide (NO\n                    <jats:sup>\n                      <jats:bold>\u2022<\/jats:bold>\n                    <\/jats:sup>\n                    ), superoxide anions (O\n                    <jats:sup>\n                      <jats:bold>\u2022<\/jats:bold>\n                    <\/jats:sup>\n                    ), and hydroxyl radicals (OH\n                    <jats:sup>\n                      <jats:bold>\u2022<\/jats:bold>\n                    <\/jats:sup>\n                    ), thereby reducing oxidative stress by decreasing inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) activity while enhancing endothelial nitric oxide synthase (eNOS) functionality to promote vasodilation and prevent hypertension. Additionally, flavonoids act as prebiotics, fostering the symbiotic gut microbiota (GM), including\n                    <jats:italic>Bifidobacteria<\/jats:italic>\n                    and\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    , which produce short\u2010chain fatty acids (SCFAs) and suppress pathogenic trimethylamine\u2010N\u2010oxide (TMAO)\u2010producing bacteria. This enhances gut epithelial barrier integrity, reduces inflammation mediated by lipopolysaccharide (LPS), and protects against heart failure, ischaemia, and atherosclerosis. Under ischemic and heart failure conditions, flavonoids inhibit apoptosis, necrosis, ferroptosis, and fibrosis by restoring hypoxia\u2010damaged mitochondrial function and cardiac energy metabolism. Furthermore, flavonoids prevent arteriosclerosis by inhibiting low\u2010density lipoprotein (LDL) oxidation, reducing cholesterol absorption, promoting bile salt\u2010hydrolysing bacteria, and decreasing vascular cell adhesion molecule (VCAM)\u20101 expression on coronary vessels. Here, we aim to advance the understanding of flavonoid\u2010mediated cardioprotection by considering their antioxidant, anti\u2010inflammatory, and gut microbiome\u2010modulating effects, offering novel insights into dietary interventions for CVD prevention and management. The findings underscore the potential of flavonoids as accessible, natural agents to address global health disparities in CVD burden.\n                  <\/jats:p>","DOI":"10.1111\/nbu.70039","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:04:56Z","timestamp":1769151896000},"page":"5-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Flavonoids and Their Influence on the Gut Microbiome: Implications for Cardiovascular Health"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5124-0598","authenticated-orcid":false,"given":"Parisa","family":"Ahmadi","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Neuromusculoskeletal Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-8456","authenticated-orcid":false,"given":"Maryam","family":"Honardoost","sequence":"additional","affiliation":[{"name":"Colorectal Research Center Iran University of Medical Sciences  Tehran Iran"},{"name":"Cardio\u2010Oncology Research Center, Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atousa","family":"Janzadeh","sequence":"additional","affiliation":[{"name":"Neuromusculoskeletal Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0655-1060","authenticated-orcid":false,"given":"Soroush","family":"Taherkhani","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0198\u20108859(99)00088\u20109"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i41.4617"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1325261"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2025.2500546"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2025.156969"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109936"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.70068"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phanu.2025.100449"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9020167"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487319870344"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2021.6436"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0101915"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13163934"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2020.112347"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7042788"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.26"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29246026"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v6.23408"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10068\u2010022\u201001058\u20103"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200404050-00002"},{"key":"e_1_2_17_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114521003627"},{"key":"e_1_2_17_23_1","doi-asserted-by":"publisher","DOI":"10.31989\/ffhd.v1i5.132"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3038"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24020346"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150804110049"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/ipd.12847"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201023571\u20104"},{"key":"e_1_2_17_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010021\u201005287\u20105"},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/frmbi.2023.1192773"},{"key":"e_1_2_17_31_1","unstructured":"Biotechnol J. 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