Dietary 3-aminobenzoic acid enhances intestinal barrier integrity and attenuates experimental colitis

Disruption of intestinal epithelial integrity and increased permeability is central to the pathogenesis of ulcerative colitis (UC). In this study, we identified 3-aminobenzoic acid (3-ABA), a dietary component abundant in azuki beans, soybeans, and chickpeas as a regulator of epithelial permeability and inflammation in the colon. Screening 119 gut microbial metabolites revealed the ability of 4-ABA, a structural isomer of 3-ABA, to enhance barrier function in Caco2 cells. Further analysis of structural isomers identified 3-ABA as the most effective, significantly increasing transepithelial electrical resistance and reducing epithelial permeability. Using liquid chromatography-mass spectrometry, 3-ABA was detected in dietary beans and human fecal samples. Fecal 3-ABA levels were significantly lower in patients with UC compared with healthy individuals. Metagenomic and functional prediction analyses revealed dysbiosis in patients with UC, characterized by an enrichment of Bacterial genes involved in ABA degradation. Gene expression analysis of 3-ABA-stimulated Caco2 cells demonstrated upregulation of tight junction molecules, such as CLDN1 and TJP1, enhancing epithelial barrier integrity. In a dextran sodium sulfate-induced colitis mouse model, rectal 3-ABA administration ameliorated colitis by enhancing epithelial barrier function and reducing inflammation. These findings highlight 3-ABA's potential as a dietary therapeutic agent for UC, offering a novel strategy to enhance intestinal integrity and mitigate inflammation.NEW & NOTEWORTHY Increased intestinal epithelial permeability is central to the pathogenesis of ulcerative colitis (UC). 3-Aminobenzoic acid (3-ABA), a dietary component abundant in beans, decreased epithelial permeability and attenuated colonic inflammation in a mouse experimental colitis model. Reduced fecal 3-ABA levels in patients with UC were associated with dysbiosis-driven accelerated degradation. These findings highlight the therapeutic potential of 3-ABA in UC by targeting colonic epithelium.

aminobenzoic acid; diet; inflammatory bowel disease; intestinal epithelium; ulcerative colitis.