Template:Tryptophan metabolism by human microbiota
{{Annotated image 4 | image = Microbiota-derived 3-Indolepropionic acid-notext.svg | link = Commons:File:Microbiota-derived 3-Indolepropionic acid.svg | header = Tryptophan metabolism by human gastrointestinal microbiota ( ) | header_align = center | header_background = #F0F8FF | align = right | image-width = 600 | image-left = 0 | image-top = 10 | width = 580 | height = 470 | alt = Tryptophan metabolism diagram | caption = {{{caption|This diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from by bacteria in the gut.[1] Indole is produced from tryptophan by bacteria that express tryptophanase.[1] Clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[2] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[1][3][4] IPA binds to the pregnane X receptor (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[1] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.[1] Lactobacillus species metabolize tryptophan into {{when pagename is|Indole-3-carboxaldehyde=indole-3-carboxaldehyde|other=indole-3-aldehyde}} (I3A) which acts on the aryl hydrocarbon receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.[1] Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[1] Indole can also be metabolized by the liver into ]], a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.[1] AST-120 (activated charcoal), an intestinal sorbent that is [[Oral administrat[[Physics:taken by mouth,Chemistry:Adsorption|adsorbs i]]ndole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.[1] }}} | annot-font-size = 14 | annot-text-align = left | annotations =
expressing
bacteria
immune
cells
↓Activation of glial cells and astrocytes
↓4-Hydroxy-2-nonenal levels
↓DNA damage
–Antioxidant
–Inhibits β-amyloid fibril formation
↑IL-22 production
↑Oxidative stress
↑Smooth muscle cell proliferation
↑Aortic wall thickness and calcification
↑Renal dysfunction
–Uremic toxin
}}
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Reflist
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions". Genome Med 8 (1): 46. April 2016. doi:10.1186/s13073-016-0296-x. PMID 27102537. "Lactobacillus spp. convert tryptophan to indole-3-aldehyde (I3A) through unidentified enzymes [125]. Clostridium sporogenes convert tryptophan to IPA [6], likely via a tryptophan deaminase. ... IPA also potently scavenges hydroxyl radicals".
Table 2: Microbial metabolites: their synthesis, mechanisms of action, and effects on health and disease
Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease - ↑ "Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites". Proc. Natl. Acad. Sci. U.S.A. 106 (10): 3698–3703. March 2009. doi:10.1073/pnas.0812874106. PMID 19234110. "Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes.".
IPA metabolism diagram - ↑ "3-Indolepropionic acid". University of Alberta. http://www.hmdb.ca/metabolites/HMDB02302. Retrieved 12 June 2018. "Indole-3-propionate (IPA), a deamination product of tryptophan formed by symbiotic bacteria in the gastrointestinal tract of mammals and birds. 3-Indolepropionic acid has been shown to prevent oxidative stress and death of primary neurons and neuroblastoma cells exposed to the amyloid beta-protein in the form of amyloid fibrils, one of the most prominent neuropathologic features of Alzheimer's disease. 3-Indolepropionic acid also shows a strong level of neuroprotection in two other paradigms of oxidative stress. (PMID 10419516) ... More recently it has been found that higher indole-3-propionic acid levels in serum/plasma are associated with reduced likelihood of type 2 diabetes and with higher levels of consumption of fiber-rich foods (PMID 28397877)
Origin: • Endogenous • Microbial" - ↑ "Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid". J. Biol. Chem. 274 (31): 21937–21942. July 1999. doi:10.1074/jbc.274.31.21937. PMID 10419516. "[Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity.".
