English: This diagram shows the metabolism of tryptophan to indole and indole derivatives in the colonic lumen.
Clostridium sporogenes metabolizes indole into
3-indolepropionic acid (IPA), a highly potent neuroprotective antioxidant. In the intestine, IPA binds to
pregnane X receptors (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function. Following
absorption and
distribution to the brain, IPA confers a neuroprotective effect against
cerebral ischemia and
Alzheimer’s disease.
Lactobacillus species metabolize indole into indole-3-aldehyde (I3A) which acts on the
aryl hydrocarbon receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production. AhR activation markedly affects in gut immunity by supporting epithelial barrier function, increasing immune tolerance to
commensal microbiota, and protecting against pathogenic infections. Indole itself acts as a
glucagon-like peptide-1 (GLP-1)
secretagogue in
intestinal L cells and as a ligand for AhR. Indole can also be metabolized by the liver to
indoxyl sulfate, a compound that is detrimental to human health in high concentrations. Accumulation of indoxyl sulfate in blood plasma is toxic and associated with vascular disease and renal dysfunction. AST-120 (
activated charcoal), an intestinal sorbent that is
taken by mouth,
adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.