REVIEW article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Flavonoids in inflammatory bowel disease: Multi-dimensional mechanisms via modulation of the intestinal barrier-microbiota-immune axis
Provisionally accepted
- 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China
- 2Southern University of Science and Technology Hospital, Shenzhen, China
- 3The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- 4China-Japan Union Hospital of Jilin University Department of Gastrointestinal and Colorectal Surgery, Changchun, China
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Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, for which the development of no vel high-efficacy, low-toxicity therapeutic strategies remains an urgent priority. Flavonoids, as natural plant-derived bioactive compounds, exhi bit unique multi-target therapeutic potential in IBD by modulating the intestinal barrier–microbiota–immune axis through multi-layered mech anisms . This review synthesizes evidence demonstrating that flavonoids: (1) Repair intestinal barrier integrity by ac tivating aryl hydrocarbon receptor (AhR) to upregulate tight junction proteins (ZO-1, occludin, claudin-5) and scave nge reactive oxygen species (ROS); (2) Reconfigure microbiota-immune crosstalk through enriching short-chain fatty acid (SCFA)-producing taxa, inhibiting pathogenic Th17 polarization while promoting Treg differentiation, and supp ressing NF-κB/NLRP3-driven inflammation; (3) Modulate immune-epigenetic networks via miRNA-mediated downreg ulation of pro-inflammatory cytokines (TNF-α, IL-6) and p53/MAPK-dependent cellular senescence regulation. (4) C linical trials highlight Flavonoids in reducing Mayo scores and endoscopic severity, paralleled by decreased serum I L-6 and fecal calprotectin. Despite low bioavailability, nanotechnology innovations—including pH/ROS-responsive na noparticles and mucoadhesive formulations—enable targeted colonic delivery and enhanced stability. Future research should prioritize multi-omics integration to decode flavonoid-host-microbiota interactomes, validate clinical translatab ility in microbiota-stratified IBD cohorts, and establish standardized bioavailability assessment frameworks. By bridgin g phytochemistry, immunology, and bioengineering, flavonoids emerge as promising multi-target agents to revolution ize dietary polyphenol-based IBD therapeutics.
Keywords: inflammatory bowel disease, Flavonoids, intestinal barrier, Microbiota-immune axis, Signaling Pathways, Nano-delivery systems
Received: 28 Jul 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Cui, Li, Dong and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhuo Liu
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