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Polyphenols and the Microbiota–Host Axis: Mechanisms of Inflammation Modulation and Cellular Protection

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

Deadline for manuscript submissions: 20 July 2026 | Viewed by 1700

Editors


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Dipartimento di Scienze Mediche, del Movimento e del Benessere, Università Partenope di Napoli, 80133 Napoli, Italy
Interests: health; polyphenols; erythrocyte; antioxidants; gut microbiota
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Guest Editor
Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University, 00166 Rome, Italy
Interests: polyphenols; oxidative stress; natural molecules; adjuvants in chemotherapy; DNA methylation; post-translational modifications of proteins

Special Issue Information

Dear Colleagues,

Dietary polyphenols, which are abundant in fruits, vegetables, cereals, tea, and wine, are powerful bioactive compounds with significant health implications. These natural compounds exert their beneficial effects through three interconnected mechanisms: modulating inflammatory pathways, protecting cellular structures from oxidative damage, and regulating the composition and function of the gut microbiota. A growing body of evidence indicates that polyphenol-induced alterations of the gut microbial ecosystem can trigger secondary metabolic pathways, amplifying their health-promoting effects beyond direct antioxidant activity.

This Special Issue aims to gather innovative, multidisciplinary research exploring the specific mechanisms by which dietary polyphenols modulate inflammation, enhance cellular resilience, and reshape the gut microbiota, thus contributing to the prevention and management of chronic diseases. We seek to integrate molecular and mechanistic studies, clinical investigations of biomarkers related to inflammatory status and cellular protection, and epidemiological evidence linking polyphenol consumption with improved health outcomes. By advancing understanding of polyphenol–microbiota–host interactions, this Special Issue aims to support evidence-based nutritional strategies and promote the rational development of polyphenol-based therapeutic approaches in health maintenance and disease prevention.

Dr. Pasquale Perrone
Dr. Laura Mosca
Guest Editors

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Keywords

  • dietary polyphenols
  • inflammation modulation
  • cellular protection
  • gut microbiota
  • anti-inflammatory effects
  • oxidative stress defense
  • microbiota-derived metabolites
  • chronic disease prevention
  • molecular mechanisms
  • nutritional
  • bioactive compounds
  • polyphenol bioavailability
  • host-microbiota interactions

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Published Papers (1 paper)

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Review

39 pages, 5125 KB  
Review
The Gut Microbiota–Polyphenol–NLRP3 Inflammasome Axis: A Key Regulatory Network Linking Diet to Chronic Inflammation
by Laura Mosca, Cristina Pagano, Maria Giovanna Tafuri, Girolamo Di Maio, Claudia M. Rejano-Gordillo, Roberta Della Marca, Stefania D’Angelo, Marcellino Monda, Giovanni Messina, Rita Polito and Pasquale Perrone
Nutrients 2026, 18(10), 1483; https://doi.org/10.3390/nu18101483 - 7 May 2026
Cited by 2 | Viewed by 1408
Abstract
Background/Objectives: Chronic low-grade inflammation, underpinned by persistent activation of the NLRP3 inflammasome, is a central pathological mechanism in non-communicable diseases including cardiovascular disease, type 2 diabetes, inflammatory bowel disease, and neurodegeneration. Dietary polyphenols have been consistently associated with reduced inflammatory burden; however, [...] Read more.
Background/Objectives: Chronic low-grade inflammation, underpinned by persistent activation of the NLRP3 inflammasome, is a central pathological mechanism in non-communicable diseases including cardiovascular disease, type 2 diabetes, inflammatory bowel disease, and neurodegeneration. Dietary polyphenols have been consistently associated with reduced inflammatory burden; however, the mechanisms underlying these effects remain incompletely understood. This review aims to characterize the gut microbiota–polyphenol–NLRP3 inflammasome axis as a central regulatory network through which diet modulates innate immune signaling and chronic inflammatory tone. Methods: A comprehensive narrative review of the available literature was conducted, integrating evidence from mechanistic studies in cell culture and animal models, microbiome research, metabolomics, and human epidemiological and interventional data. Results: The gut microbiota emerges as a critical biochemical intermediary that transforms dietary polyphenols into bioactive metabolites, including urolithins, phenyl-γ-valerolactones, protocatechuic acid, and short-chain fatty acids, with enhanced bioavailability and potent inflammasome-modulating properties. These compounds suppress NLRP3 activation through multiple converging mechanisms, including inhibition of NF-κB-dependent priming, mitochondrial quality control via mitophagy, Nrf2-mediated antioxidant responses, and HDAC inhibition. Evidence across cardiovascular, metabolic, neurological, and respiratory disease models supports the translational relevance of this axis. Conclusions: The microbiota–polyphenol–NLRP3 axis functions as an integrated, self-regulated network in which each component simultaneously shapes and is shaped by the others: dysbiosis primes NLRP3 and depletes protective metabolites, while inflammasome hyperactivation further destabilises microbial ecology; polyphenol biotransformation by specific taxa interrupts this feed-forward loop at multiple nodes, restoring homeostasis. Full article
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