Indol-3-Carbinol ameliorates colitis in mice by AhR-mediated production of antimicrobial peptides and mucins

Abstract Indole-3-carbinol (I3C) is a dietary compound that acts as ligand for the aryl hydrocarbon receptor (AhR), an important sensor environmental polyaromatic chemicals and regulator of immune response. The pathogenesis colitis involves multiple interactions between microbial dysbiosis, dysregulation host response, factors, genetic profile. Indeed, studies have shown defective expression AhR antimicrobial peptides (AMPs) particularly defensins in inflammatory bowel disease (IBD) patients. Here, we investigated how I3C influences production AMPs, b-defensins, through colonic microbiota composition Anti-CD40 or dextran sulfate sodium (DSS)-induced colitis. Our analysis found attenuates activation leading to increased murine b-defensins (mBDs) by Colonic Epithelial Cells, resulting restoration healthy gut prevention inflammation. We analyzed AMPs mucins. significantly mRNA AhR, such mBDs, Reg4, mucins, when compared vehicle-treated mice with Similarly, levels mucins were DSS+I3C-treated colon adenocarcinoma cells MC-38 (murine) Caco2 (human) DSS-treated cells. To conclude, our findings demonstrate inhibits primarily AhR-mediated induction protective enrichment (This work was supported part NIH grants R01ES030144, P01AT003961, P20GM103641, R01AI123947, R01AI160896). This R01AI160896