Microbiota-derived tryptophan metabolites

About 5 % of tryptophan is catabolized by the gut microbome, generating so-called microbiome-derived tryptophan metabolites, which include indole (IND), 3-indoxyl sulfate (3IS), and indole derivatives, such as indole-3-acetamide (IAM), indole-3-acetate (IAA), indole-3-acetaldehyde (IAAld), indole-3-aldehyde (IAld), indole-3-acrylate (IacA) and indole-3-propionate (IPA).
Microbiome-derived tryptophan metabolites have diverse biological roles affecting health (Figure 1). Some are ligands of the aryl hydrocarbon receptor (AhR) thereby modulating the immune response, others have anti-inflammatory and anti-oxidative effects, enhance the intestinal epithelial barrier, increase secretion of gut hormones and stimulate intestinal motility. Indoles are generally thought to mediate beneficial health effects, with the exception of 3IS, a host-microbial co-metabolite generated from indole in the liver; 3IS is toxic at high concentrations and associated with vascular disease and renal dysfunction. 3IS is considered as uremic toxin, which is highly (90 %) bound to albumin, and therefore accumulates despite regular hemodialysis (2).