{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:28:23Z","timestamp":1792114103068,"version":"4.4.0"},"reference-count":236,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases aglycone forms that may cross the gut barrier. A significant proportion of polyphenols escapes absorption and reaches the colon, where resident microbes convert them into simpler phenolic metabolites. Such molecules are often more bioavailable than the parent compounds and can enter systemic circulation, leading to distant effects. Although higher polyphenol consumption has been associated with preventive and therapeutic outcomes, even low intake or poor intestinal absorption may still confer benefits, as polyphenols in the colon can positively modulate gut microbiota composition and function, contributing to favorable shifts in the microbial metabolome. These interactions can influence host metabolic, immune, and neurological pathways, particularly through the gut\u2013liver\u2013brain axis. To provide a comprehensive understanding of these relationships, this review examines the dose-related activity of polyphenols, their microbiota-mediated biotransformation, their bioavailability, and the health effects of their metabolites, while also presenting a comparative overview of key studies in the field. We underscore the importance of integrating microbiome and polyphenol research to recapitulate and contextualize the health benefits of dietary polyphenols.<\/jats:p>","DOI":"10.3390\/nu17172793","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"2793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Unlocking Polyphenol Efficacy: The Role of Gut Microbiota in Modulating Bioavailability and Health Effects"],"prefix":"10.3390","volume":"17","author":[{"given":"Laura","family":"Mahdi","sequence":"first","affiliation":[{"name":"Clinical Medica A. Murri, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Graziani","sequence":"additional","affiliation":[{"name":"Institut AllergoSan Pharma GmbH, 8055 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-0400","authenticated-orcid":false,"given":"Gyorgy","family":"Baffy","sequence":"additional","affiliation":[{"name":"Department of Medicine, VA Boston Healthcare System, Boston, MA 02132, USA"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0938-3011","authenticated-orcid":false,"given":"Emilie K.","family":"Mitten","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Clinical Medica A. Murri, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5943-9531","authenticated-orcid":false,"given":"Mohamad","family":"Khalil","sequence":"additional","affiliation":[{"name":"Clinical Medica A. Murri, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Khalil, M., Di Ciaula, A., Mahdi, L., Jaber, N., Di Palo, D.M., Graziani, A., Baffy, G., and Portincasa, P. (2024). Unraveling the Role of the Human Gut Microbiome in Health and Diseases. 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