Microbiome & Chronic Diseases

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Tryptophan ⇒ Indole {90000233}

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Shared Reference Notes

  • [1.1] [#Crohn’s disease, #Inflamatory bowel disease
    - The blood–brain barrier allows the access of #Tryptophan. - In IBD, especially in CD patients, TRP metabolism increases; consequently, the amino acid levels are reduced with respect to normal healthy individuals, and these changes correlate with the gravity of the disease. - TRP undergoes two major metabolic host pathways, the #kynurenine (KYN) and #Serotonin (5-HT) biosynthetic pathways, and one microbial pathway to produce indole and its derivatives.
  • [1.2
    - #Tryptophan and #Phenylalanine > Microbiom Catabolism > increased #Phenol and indole derivatives > chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity.
  • [1.3] [#Pancreatic Cancer] [#Lactobacillus] [#Tryptophan] [#Probiotic
  • [1.4] [#Colorectal cancer] [#Tryptophan
    - Around 5% of Trp > metabolized by gut bacteria into indole and indolic compounds > can bind to pregnane X receptors (PXR) and aryl hydrocarbon receptor (AhR) > promote intestinal homeostasis, enhance barrier function and tight junctions, reduce permeability, regulate intestinal immune tolerance. - Alteration in Trp metabolism begin at early stages of CRC and allow immune evasion umor microenvironment (i.e. the oncogene c-MYC cab accelerate Trp uptake) with an increase in IDO1 and T cell inactivation. - Reduction in indoles production is observed in CRC and the administration of microbial indolic metabolites, diindolylmethane or I3C (AhR ligands), reduces tumor formation
  • [1.5
    - #Lactococcus lactis species within Lactococcus can produce TRP 2,3-dioxygenase that metabolizes TRP into KYN, while both #Lactococcus lactis and #Streptococcus thermophilus species can produce aromatic-amino-acid transaminase that metabolizes TRP into indole-3-lactate.
  • [1.6] [#Chronic kidney disease
    - Bacterial species involved in #Butyrate production, indole synthesis and mucin degradation were also related to CKD.
  • [1.7
    - #Chronic kidney disease > decreased Indole, indole-3-carboxaldehyde and indole-3-propionic acid
  • - #kynurenine and indole derivatives might be associated with neurogenic #Depression
  • - indole has antipathogenic potential toward #Salmonella by reducing the expression of virulence genes. - Indole also exerts anti-inflammatory properties by counteracting the lipopolysaccharide (LPS)-induced inflammatory response and inhibiting pro-inflammatory activation of macrophages.
  • [#Short Chain Fatty Acid] - SCFAs, #Serotonin, #kynurenine, indole and its derivatives, and #Tryptamine, can bridge the gut and nervous system.
  • [1.8] [#Indole-3-propionic acid (IPA), #Indole-3-aldehyde (I3A) (IAID)
    - Most #Tryptophan is transformed in the indole pathway. Intestinal bacteria express the enzyme tryptophanase, leading to the production of indole in the gut. - Indole > metabolized into 3-indolepropionic acid (IPA) > binds to the pregnane X receptor (PXR) in intestinal cells. - IPA is absorbed in the intestine and distributed to the brain > neuroprotective properties. - Indole > metabolized into indole-3-aldehyde (I3A) > triggers immunoprotective effects in the intestine.
  • - In the liver, indole may be metabolized into #Indoxyl sulfate, which can be toxic in high concentrations.
  • [1.9] [#Diabetes Type 2] [#Indole-3-propionic acid (IPA), #Indole sulfuric acid (ISA)
    - The bacterially derived Trp metabolites indoles, IPA and indole sulfuric acid (ISA) are lower in blood samples from subjects with type 2 diabetes as compared to the lean controls. - Higher serum concentrations of IPA are also associated with a reduced prevalence of T2D.
  • - Bacterial species such as Bacteroides ovatus, Clostridium limosum, Enterococcus faecalis and Escherichia coli are able to convert Trp into indole. - Indole modulates the secretion of glucagon-like peptide-1 (GLP-1) in mouse colonic enteroendocrine L cells, which is critical in stimulating the insulin secretion of pancreatic β cells, suppressing appetite and slowing gastric emptying.
  • [#Tryptophan] - There are decreased circulating levels of AhR agonists in individuals with #Multiple Sclerosis.
  • [#Serotonin] - #Pu-erh tea could boost the indole and 5-hydroxytryptamine pathways of the Trp metabolism.
  • [#Indole-3-propionic acid (IPA), #Indole-3-acetic acid (IAA), #Indole-3-aldehyde (I3A) (IAID), #Indole-3-lactic acid (ILA), #Indoleacrylic acid (IA), #Indole-3-acetamide (IAM), #Indole-3-pyruvic acid (IPyA)] - For AhR, the most effective Trp metabolites are indole, #Skatole, IA, #Tryptamine, IPyA and indole-3-acetamide (IAM), whereas IAA, IAID, IPA and ILA are the least active
  • [#Colorectal cancer] - Indole derivates support gut homeostasis by promoting epithelial barrier function and immune tolerance, which are important to suppress carcinogenesis in the colon
  • [#Colorectal cancer] - #Tryptophan metabolism is altered in CRC with a shift towards increased Kyn production by host cells but decreased indole production by gut microbes. - Elevated fecal Kyn to #Tryptophan ratios but decreased indole to tryptophane ratios were found in patients with colorectal neoplastic lesions.
  • - Many common gut bacteria are capable of producing indoles and the fecal indole concentration ranges between 1 and 4 mM. - Common indole metabolites include indole-3-pyruvate, indole-3-acetaldehyde, indole-3-lactic acid, indole-3-acetic acid, indole-3-acetamide, and indole-3-propionic acid. - Indoles are recognized by PXR and the acryl hydrocarbon receptor (AhR), which are expressed by various cell types including intestinal epithelial and immune cells. - Dietary indoles, found in cruciferous vegetables, also function as AhR ligands.
  • [#kynurenine] - The host Kyn and bacterial indole pathways each process ~90% and ~5% of the available #Tryptophan, respectively.
  • [#Polyamine] - Amino acids that reach the colon are converted by the microbiome to polyamines or indole derivates. - The most common polyamines are #Putrescine, #Spermidine, and #Spermine, which play important roles in cell growth, proliferation, and migration.
  • - #Tryptophan metabolites are produced via four different pathways: The #Serotonin pathway, the #Tryptamine pathway, the #kynurenine pathway, and the bacterial indole pathway.

References Notes

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