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Dose-Related Activity of Polyphenols: Physiological Interaction with Gut Microbiota

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 3209

Special Issue Editors


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Guest Editor
Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy
Interests: polyphenols; nutritional phytochemicals; gut microbiota; metabolic disturbances; metabolism
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Guest Editor
Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy
Interests: lipid metabolism; enterohepatic circulation; liver steatosis; gut microbiota; polyphenols

Special Issue Information

Dear Colleagues,

Polyphenols are among the most extensively studied nutritional phytochemicals due to their potential beneficial effects on human health. Over recent years, significant advancements have deepened our understanding of their mechanisms of action, bioavailability, and interactions with biological systems. One particularly dynamic area of research is the dose-dependent activity of polyphenols and their complex interplay with gut microbiota, which significantly influences their metabolism and biological effects.

This Special Issue offers a comprehensive exploration of the intricate relationships between polyphenol dosage, their bioactivities, and their modulation of gut microbial communities. Moving beyond a narrow focus on individual polyphenol compounds or isolated health outcomes, this Issue aims to provide a broad perspective on current research. Topics of interest include, but are not limited to, the following:

  • Dose–response effects of polyphenols on human health outcomes.
  • Biotransformation of polyphenols by gut microbiota and its impact on bioactivity.
  • Reciprocal interactions between polyphenols and gut microbial composition or functionality.
  • Clinical and preclinical evidence of dose-specific polyphenol effects mediated by the gut microbiome.
  • Methodological advances for studying dose-dependent polyphenol–microbiota interactions.

By highlighting the synergistic and dose-specific effects of polyphenols in the context of gut microbiota, this Issue seeks to expand our understanding of their role in human health and encourage innovative research at the intersection of nutrition, microbiology, and pharmacology.

Dr. Mohamad Khalil
Prof. Dr. Piero Portincasa
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polyphenols
  • gut microbiota
  • dose–response relationship
  • biotransformation
  • microbiome–polyphenol interactions
  • nutritional phytochemicals

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Published Papers (1 paper)

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Review

35 pages, 16363 KB  
Review
Unlocking Polyphenol Efficacy: The Role of Gut Microbiota in Modulating Bioavailability and Health Effects
by Laura Mahdi, Annarita Graziani, Gyorgy Baffy, Emilie K. Mitten, Piero Portincasa and Mohamad Khalil
Nutrients 2025, 17(17), 2793; https://doi.org/10.3390/nu17172793 - 28 Aug 2025
Viewed by 2808
Abstract
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 [...] Read more.
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–liver–brain 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. Full article
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