Gallic Acid Protects Against DSS‐Induced Colitis by Modulating Gut Microbiota and Suppressing the Activation of NF‐κB/MAPK Signaling Pathway

To investigate the protective role and mechanisms of gallic acid (GA) against ulcerative colitis (UC), C57BL/6 mice were pretreated with GA (10 or 50 mg/kg) or saline for 21 days before colitis induction with 2.5% DSS for 7 days. An in vitro Caco-2/RAW 264.7 coculture model mimicking the intestinal epithelium was used. After 24-h GA pretreatment, inflammation was induced with LPS in Caco-2/RAW 264.7 coculture cell for 4 h. GA alleviated colitis symptoms, improving body weight, preventing colon shortening, reducing histopathological damage, and lowering pro-inflammatory cytokines (IL-6, IL-22, TNF-α, IL-17α). It enhanced intestinal barrier integrity by upregulating tight junction (TJ) proteins claudin-1 and occludin. Mechanistically, GA inhibited NF-κB and MAPK pathways by suppressing phosphorylation of p65, IκB, JNK, ERK, and P38 in colon tissue. GA also favorably modulated the gut microbiome, reducing pathobionts (e.g., Desulfovibrio) and enriching beneficial genera like Enterobacteria and Prevotella. In the cell coculture model, GA suppressed LPS-induced pro-inflammatory mediators, upregulated IL-10, and restored LPS-downregulated TJ protein expression. These findings indicate that GA alleviates DSS-induced UC by restoring intestinal homeostasis, exerting anti-inflammatory effects, and providing preventive benefits upon long-term use, supporting its potential as a prophylactic agent for UC.