Gut microbiota‐derived butyrate mediates the anticolitic effect of indigo supplementation through regulating CD4⁺ T cell differentiation

This study explored the effect of plant-derived indigo supplementation on intestinal inflammation using in vivo, in vitro, and clinical sample analyses. Our results showed that indigo decreased mucosal inflammation by regulating CD4⁺ T cell differentiation in a gut microbiota-dependent manner. Microbes transferred from indigo-treated mice, indigo-induced enrichment of <i>Roseburia intestinalis</i>, and its metabolite butyrate played a role in Th17/Treg immunity similar to that of indigo in intestinal inflammation, which was involved in mTORC1/HIF-1α signal-mediated reprogrammed glucose metabolism. We further showed that patients with ulcerative colitis exhibited significant gut dysbiosis and CD4⁺ T cell differentiation abnormalities. Our findings provide new insights into the gut-immune axis in ulcerative colitis, offering a novel microbial-based immunotherapy for the treatment of inflammatory bowel disease.