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Microbiota-derived 3-Indolepropionic acid-notext

Image of Clostridium

Description:

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.

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