预防性与治疗性白藜芦醇在调节肠道微生物群和减轻葡聚糖硫酸钠（DSS）诱导的结肠炎炎症方面的比较疗效。

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

作者信息

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

机构信息

Guangxi Medical University, Nanning, 530021, Guangxi, China.

Department of Neurosurgery, Wuming Hospital of Guangxi Medical University, Wuming, 530199, Guangxi, China.

出版信息

BMC Immunol. 2025 May 28;26(1):42. doi: 10.1186/s12865-025-00718-3.

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.

背景

由于预防策略有限以及白藜芦醇（RSV）等治疗药物的生物利用度较低，炎症性肠病（IBD）的管理仍然具有挑战性。虽然RSV具有抗炎特性，但其通过调节肠道微生物群的预防潜力尚未得到探索。

方法

使用2.5%的葡聚糖硫酸钠（DSS）建立小鼠结肠炎模型，将小鼠随机分为对照组（CON）、DSS组、治疗性RSV治疗组（RSV）和预防性RSV治疗组（PRE）。系统评估临床结局、肠道屏障完整性、炎性细胞因子、巨噬细胞极化、TLR4/NF-κB信号传导和肠道微生物群（16S rRNA测序）。

结果

在所有指标上，预防性RSV（PRE）均优于治疗性RSV。PRE将结肠炎严重程度降低了51.4%（体重减轻，与RSV相比P < 0.001），并恢复了黏膜结构（与DSS相比P = 0.048）。从机制上讲，PRE通过转录（紧密连接蛋白1：为CON组的56.7%；闭合蛋白：与DSS相比诱导增加14倍）和蛋白质水平恢复（紧密连接蛋白1：为CON组的96.5%，P = 0.02）使屏障功能正常化，抑制促炎细胞因子（肿瘤坏死因子-α：80.8%；白细胞介素-6：69.9%；白细胞介素-18：>96%，与DSS相比P < 0.001），并通过抑制TLR4/NF-κB（TLR4降低53%，而RSV为15%，P < 0.001）促进M2巨噬细胞极化（甘露糖受体：与CON组相比增加1.7倍，P = 0.02）。尽管RSV和PRE之间的α多样性相当，但PRE独特地富集了具有屏障保护作用的分类群（乳酸乳球菌、穆里杆菌属）并恢复了微生物氨基酸生物合成。至关重要的是，尽管全身生物利用度较低，但PRE的疗效表明微生物群介导的“腔内启动”是其主要机制。