Dysregulation of the gut microbiota and microbially derived metabolite production has been associated with metabolic disorders. Using metabolomics, Koh et al. identify levels of the amino acid-derived metabolite imidazole propionate to be elevated in the portal and peripheral blood of subjects with type 2 diabetes. Using an in vitro gut simulator, imidazole propionate was found to be a histidine-derived metabolite produced from microbial communities specific to subjects with type 2 diabetes. When injected into mice, imidazole propionate impaired glucose tolerance and insulin signalling.