Polyphenols as next-generation prebiotics targeting intestinal mucosal tolerance
5 affiliations
- 1Institute of Pharmacology & Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
- 2Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), University of Coimbra, Coimbra, Portugal
- 3Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Chemical Engineering and Renewable Resources for Sustainability (CERES), Department of Chemical Engineering, University of Coimbra, Coimbra, Portugal
- 4CBQF - Center for Biotechnology and Fine Chemistry, Associated Lab., School of Biotechnology, Catholic University, Porto, Portugal
- 5Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal; Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT)-Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal; Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Abstract
Polyphenols, long recognized for their antioxidant and anti-inflammatory properties, are widely consumed as dietary components or as constituents of functional foods and nutraceuticals. Emerging evidence, however, supports a paradigm shift beyond a purely redox-centered perspective, repositioning polyphenols as functionally relevant prebiotic phytochemicals with significant immunomodulatory capacity. This review frames polyphenols as next-generation prebiotics, emphasizing their capacity to act through coordinated, multi-layered mechanisms that extend beyond the stimulation of intestinal microbial growth. It examines how the gut ecosystem leverages their low systemic bioavailability and explores mechanisms linking their health benefits to microbiota-mediated intestinal mucosal tolerance as interconnected dimensions of prebiotic functionality. Emphasis is placed on the multimodal actions of polyphenol-derived microbial metabolites, increasingly recognized as bona fide postbiotics with therapeutic potential. These metabolites modulate key functional microbial outputs, including the secretion and cargo of bacterial extracellular vesicles, thereby regulating tolerogenic immune responses across the epithelial layer, lamina propria, Peyer's patches, and mesenteric lymph nodes. This integrated mode of action clearly distinguishes polyphenols from classical carbohydrate-based prebiotics, positioning them within a candidate functional category capable of targeting immune pathways in autoimmune and inflammatory diseases, including inflammatory bowel disease, diabetes and food allergies. The review further explores polyphenol-based prebiotic interventions driven by microbial functionality rather than taxonomic composition alone and highlights challenges and opportunities of polyphenols as tools in precision immunonutrition protocols where interventions are tailored to individual metabotypes, health status and metabolic variability.
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BibTeX
@article{ferreira2026polyphenols,
title = {{Polyphenols as next-generation prebiotics targeting intestinal mucosal tolerance}},
author = {Carolina Ferreira and Pedro Vieira and Artur Figueirinha and Lígia Salgueiro and Maria Manuela Pintado and João Oliveira Malva and Miguel Castelo Branco and Flávio Reis and Sofia Viana},
journal = {Biomedicine \& Pharmacotherapy},
year = {2026},
month = jun,
doi = {10.1016/j.biopha.2026.119592},
url = {https://doi.org/10.1016/j.biopha.2026.119592},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Polyphenols as next-generation prebiotics targeting intestinal mucosal tolerance
AU - Carolina Ferreira
AU - Pedro Vieira
AU - Artur Figueirinha
AU - Lígia Salgueiro
AU - Maria Manuela Pintado
AU - João Oliveira Malva
AU - Miguel Castelo Branco
AU - Flávio Reis
AU - Sofia Viana
PY - 2026
DA - 2026/06/06
JO - Biomedicine & Pharmacotherapy
DO - 10.1016/j.biopha.2026.119592
UR - https://doi.org/10.1016/j.biopha.2026.119592
AB - Polyphenols, long recognized for their antioxidant and anti-inflammatory properties, are widely consumed as dietary components or as constituents of functional foods and nutraceuticals. Emerging evidence, however, supports a paradigm shift beyond a purely redox-centered perspective, repositioning polyphenols as functionally relevant prebiotic phytochemicals with significant immunomodulatory capacity. This review frames polyphenols as next-generation prebiotics, emphasizing their capacity to act through coordinated, multi-layered mechanisms that extend beyond the stimulation of intestinal microbial growth. It examines how the gut ecosystem leverages their low systemic bioavailability and explores mechanisms linking their health benefits to microbiota-mediated intestinal mucosal tolerance as interconnected dimensions of prebiotic functionality. Emphasis is placed on the multimodal actions of polyphenol-derived microbial metabolites, increasingly recognized as bona fide postbiotics with therapeutic potential. These metabolites modulate key functional microbial outputs, including the secretion and cargo of bacterial extracellular vesicles, thereby regulating tolerogenic immune responses across the epithelial layer, lamina propria, Peyer's patches, and mesenteric lymph nodes. This integrated mode of action clearly distinguishes polyphenols from classical carbohydrate-based prebiotics, positioning them within a candidate functional category capable of targeting immune pathways in autoimmune and inflammatory diseases, including inflammatory bowel disease, diabetes and food allergies. The review further explores polyphenol-based prebiotic interventions driven by microbial functionality rather than taxonomic composition alone and highlights challenges and opportunities of polyphenols as tools in precision immunonutrition protocols where interventions are tailored to individual metabotypes, health status and metabolic variability.
SN - 0753-3322
SN - 1950-6007
ER -