Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23

Both genetic predisposition and environmental factors appear to play a role in inflammatory bowel disease (IBD) development. Genetic studies in humans have linked the interleukin (IL)-23 signaling pathway with IBD, but the environmental factors contributing to disease have remained elusive. Here, we show that the azo dyes Red 40 and Yellow 6, the most abundant food colorants in the world, can trigger an IBD-like colitis in mice conditionally expressing IL-23, or in two additional animal models in which IL-23 expression was augmented. Increased IL-23 expression led to generation of activated CD4+ T cells that expressed interferon-γ and transferred disease to mice exposed to Red 40. Colitis induction was dependent on the commensal microbiota promoting the azo reduction of Red 40 and generation of a metabolite, 1-amino-2-naphthol-6-sulfonate sodium salt. Together these findings suggest that specific food colorants represent novel risk factors for development of colitis in mice with increased IL-23 signaling. [Display omitted] •Food colorants Red 40 and Yellow 6 induce colitis in mice overexpressing IL-23•Elevated IL-23 induces development of pathogenic CD4+ T cells that produce IFN-γ•Commensal bacteria such as B. ovatus and E. faecalis metabolize Red 40•ANSA-Na, a metabolite of Red 40 and Yellow 6, induces relapse of colitis He et al. find that food colorants Red 40 and Yellow 6 induce colitis in mice with dysregulated expression of IL-23. Colitis development requires bacterial processing of the food colorants and is dependent on IL-23-induced pathogenic CD4+ T cells that produce IFN-γ.