Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis
Abstract 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 r...
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2025-05-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-025-00718-3 |
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| author | Senmei Qin Zongjing Yang Jinqing Lei Qingli Xie Linsui Jiang Yuanyuan Fan Yonggu Luo Kecong Wei Wei Luo Bing Yu |
| author_facet | Senmei Qin Zongjing Yang Jinqing Lei Qingli Xie Linsui Jiang Yuanyuan Fan Yonggu Luo Kecong Wei Wei Luo Bing Yu |
| author_sort | Senmei Qin |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-0a048f3947ab4de0a5078991c7cceeec |
| institution | DOAJ |
| issn | 1471-2172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Immunology |
| spelling | doaj-art-0a048f3947ab4de0a5078991c7cceeec2025-08-20T03:22:12ZengBMCBMC Immunology1471-21722025-05-0126111610.1186/s12865-025-00718-3Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitisSenmei Qin0Zongjing Yang1Jinqing Lei2Qingli Xie3Linsui Jiang4Yuanyuan Fan5Yonggu Luo6Kecong Wei7Wei Luo8Bing Yu9Guangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityDepartment of Neurosurgery, Wuming Hospital of Guangxi Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical UniversityAbstract 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.https://doi.org/10.1186/s12865-025-00718-3ResveratrolInflammatory bowel diseaseGut microbiotaMacrophage polarizationTLR4/NF-κB pathway |
| spellingShingle | Senmei Qin Zongjing Yang Jinqing Lei Qingli Xie Linsui Jiang Yuanyuan Fan Yonggu Luo Kecong Wei Wei Luo Bing Yu Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis BMC Immunology Resveratrol Inflammatory bowel disease Gut microbiota Macrophage polarization TLR4/NF-κB pathway |
| title | Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis |
| title_full | Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis |
| title_fullStr | Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis |
| title_full_unstemmed | Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis |
| title_short | Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis |
| title_sort | comparative efficacy of preventive vs therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in dss induced colitis |
| topic | Resveratrol Inflammatory bowel disease Gut microbiota Macrophage polarization TLR4/NF-κB pathway |
| url | https://doi.org/10.1186/s12865-025-00718-3 |
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