Quercetin boosts gut microbiota-driven production of isovanillic acid to alleviate colitis via enhancing intestinal barrier function

Ulcerative colitis (UC) is a severe inflammatory bowel disease marked by intestinal inflammation, compromised barrier function, and gut microbiota imbalance, with a restricted range of therapeutic options currently available. Quercetin, a flavonoid extracted from fruits and vegetables, have been shown significant anti-inflammatory and microbiota-modulating effects. However, the interactions between gut microbes and quercetin in colitis remain insufficiently elucidated. This research delved into the potential involvement of the gut microbiota-isovanillic acid (IVA)-intestinal barrier axis in the anti-colitis effects of quercetin via 16S rDNA sequencing and metabolomics. Quercetin administration effectively enhanced gut barrier integrity and mitigated colitis by boosting IVA production through modulating gut microbiota composition, particularly increasing Clostridium_XIVa and Clostridium_XI abundances. Notably, gut microbiota depletion with antibiotics (ABX) treatment markedly diminished IVA production and concurrently negated quercetin's positive effects on colitis. More importantly, IVA supplementation was also effective in alleviating colitis via enhancing gut barrier function, suggesting gut microbiota-derived IVA supported beneficial effects of quercetin on colitis. Our research highlighted the crucial involvement of gut microbial-derived IVA in the anti-colitis effects of quercetin and underscored its therapeutic potential, along with IVA, as a treatment for colitis and other intestinal inflammatory conditions.