Resveratrol may ease brain and mood problems linked to IBD by changing gut bacteria metabolism and promoting protective brain immune cells through the gut-brain connection
reduced colitis-associated anxiety- and depression-like behaviors in mice while reshaping microbiota, arginine metabolism, barrier markers, inflammation, and microglial polarization.
Evidence
This DSS-induced colitis mouse study tested RSV at 100 mg/kg/day and integrated behavioral, barrier, inflammatory, microbiome, metabolite, and neuroimmune measurements.
Caveat
The abstract reports a mouse disease model with multi-omics correlations, so it does not prove efficacy for human IBD-related neuropsychiatric complications.
Simplified
UNLABELLED: Inflammatory bowel disease (IBD) is intricately linked to neuropsychiatric comorbidities through dysregulation. This study demonstrates that (RSV), a natural polyphenol, alleviates DSS-induced colitis-associated anxiety and depression by reprogramming the microbiota─metabolite-barrier network. RSV (100 mg/kg/day) ameliorated DSS-associated anxiety-like behaviors in open field tests (peripheral zone time ↓12.6%,< 0.0001) and depression-like phenotypes (TST immobility ↓31.0%,= 0.0004). It restored colonic barrier integrity via ZO-1 mRNA upregulation (↑80.4%,< 0.0001) and PAS score recovery (↑29.6%,< 0.0001), while reducing systemic inflammation (serum LPS ↓31.9%, TNF-α ↓29.9%;< 0.0001) vs. DSS. Crucially, RSV attenuated neuroinflammation by enhancing brain ZO-1 protein expression (↑146.1%,= 0.0016), suppressing TLR4/MyD88/NF-κB signaling (TLR4 mRNA ↓68.8%, MyD88 protein ↓48.8%;< 0.05), and promoting M2 microglial polarization (CD206 protein ↑171.9%,= 0.0003) vs. DSS. Multi-omics integration revealed RSV's dual regulatory mechanism: ① Suppression of the pro-inflammatory(↓42% and ↓37%, respectively;< 0.01), disrupting LPS─TLR4─MyD88 cascades; ② Enrichment of barrier-protective(↑419%) and(↑208%), driving polyamine synthesis (spermidine ↑92%, spermine ↑38%) vs. DSS to reinforce gut-brain barriers. Spearman correlations confirmed-4-guanidinobutanoic acid-LPS-MyD88 interactions(r = 0.658-0.865) and-spermine-ZO-1 associations (r = 0.539-0.725). Conclusions: These findings establish RSV as a microbiota-metabolite modulator that redirects arginine metabolism from a pro-inflammatory bypass to polyamine-mediated barrier repair, offering novel therapeutic strategies for IBD-related neuropsychiatric complications. The integrated "microbe-metabolite-neuroimmune" axis provides mechanistic insights into gut-brain crosstalk, emphasizing dual-barrier restoration as a critical intervention node. P P P P P P P P Turicibacter4-guanidinobutanoic acid axis P Muribaculum Dubosiella Turicibacter Dubosiella
GRAPHICAL ABSTRACT: Resveratrol (RSV) alleviates psychiatric comorbidities in dextran sulfate sodium (DSS)-induced colitis mice by inhibiting the "" axis and activating the "" repair axis. This results in the restoration of gut-brain barrier integrity, reduction of inflammation, and regulation of microglial M2 polarization. [Image: see text] Turicibacter-4-Guanidinobutanoic Acid-MyD88Muribaculum/Dubosiella-polyamine-ZO-1
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02448-w.
Key numbers
12.6%
Decrease in Anxiety-like Behavior
Time spent in the peripheral zone of the open field test vs. .
31.0%
Reduction in Immobility Time
Immobility time in the tail suspension test vs. .
80.4%
Increase in ZO-1 mRNA Levels
Comparison of ZO-1 mRNA levels in colon tissue vs. .
Full Text
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The authors declare that they have no known competing financial interests or personal relationships that could appear to have influenced the work reported in this paper.
