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Background <p>Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored.</p> Methods <p>A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated.</p> Results <p>Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, <i>P</i> &lt; 0.001 vs. RSV) and restored mucosal architecture (<i>P</i> = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, <i>P</i> = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: &gt;96%, <i>P</i> &lt; 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, <i>P</i> = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, <i>P</i> &lt; 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (<i>Lactococcus</i>, <i>Muribaculum</i>) and restored microbial amino acid biosynthesis. Crucially, PRE’s efficacy despite low systemic bioavailability implicated microbiome-mediated “luminal priming” as its primary mechanism.</p> Conclusions <p>This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative “food as medicine” strategy for IBD, highlighting RSV’s potential as a chronotherapeutic agent to reshape clinical paradigms.</p>

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Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月28日

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  • Senmei Qin,
  • Zongjing Yang,
  • Jinqing Lei,
  • Qingli Xie,
  • Linsui Jiang,
  • Yuanyuan Fan,
  • Yonggu Luo,
  • Kecong Wei,
  • Wei Luo,
  • Bing Yu

摘要

Background

Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored.

Methods

A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated.

Results

Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, P < 0.001 vs. RSV) and restored mucosal architecture (P = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, P = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: >96%, P < 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, P = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, P < 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (Lactococcus, Muribaculum) and restored microbial amino acid biosynthesis. Crucially, PRE’s efficacy despite low systemic bioavailability implicated microbiome-mediated “luminal priming” as its primary mechanism.

Conclusions

This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative “food as medicine” strategy for IBD, highlighting RSV’s potential as a chronotherapeutic agent to reshape clinical paradigms.