{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:38:58Z","timestamp":1791589138876,"version":"4.3.4"},"reference-count":168,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"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>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\u2013polyphenol\u2013NLRP3 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-\u03b3-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-\u03baB-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\u2013polyphenol\u2013NLRP3 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.<\/jats:p>","DOI":"10.3390\/nu18101483","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:03:37Z","timestamp":1778144617000},"page":"1483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Gut Microbiota\u2013Polyphenol\u2013NLRP3 Inflammasome Axis: A Key Regulatory Network Linking Diet to Chronic Inflammation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-9192","authenticated-orcid":false,"given":"Laura","family":"Mosca","sequence":"first","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-6595","authenticated-orcid":false,"given":"Cristina","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Tafuri","sequence":"additional","affiliation":[{"name":"Department of Literary, Pegaso University, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-2092","authenticated-orcid":false,"given":"Girolamo","family":"Di Maio","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Sciences, Pegaso Telematic University, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-5975","authenticated-orcid":false,"given":"Claudia M.","family":"Rejano-Gordillo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5955-4495","authenticated-orcid":false,"given":"Roberta","family":"Della Marca","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7585-5052","authenticated-orcid":false,"given":"Stefania","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Medical, Movement, and Wellbeing Sciences, Parthenope University of Naples, 80133 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-218X","authenticated-orcid":false,"given":"Marcellino","family":"Monda","sequence":"additional","affiliation":[{"name":"Unit of Dietetics and Sports Medicine, Section of Human Physiology, Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Messina","sequence":"additional","affiliation":[{"name":"Unit of Dietetics and Sports Medicine, Section of Human Physiology, Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1313-2574","authenticated-orcid":false,"given":"Rita","family":"Polito","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Sciences, Pegaso Telematic University, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5627-0267","authenticated-orcid":false,"given":"Pasquale","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Sciences, Pegaso Telematic University, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1152\/physiol.00021.2024","article-title":"Low-Grade Chronic Inflammation: A Shared Mechanism for Chronic 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