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Summary
DescriptionMicrobiota-derived 3-Indolepropionic acid.jpg |
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. |
Date | |
Source | (April 2016). "Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions". Genome Med 8 (1): 46. DOI:10.1186/s13073-016-0296-x. PMID 27102537. PMC: 4840492. Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease |
Author | Zhang LS, Davies SS |
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current | 07:09, 27 June 2016 | 779 × 609 (100 KB) | Seppi333 | removed "see table 1" text | |
06:41, 27 June 2016 | 779 × 609 (85 KB) | Seppi333 | User created page with UploadWizard |
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