Indole-3-acetic acid {90000173}

Shared Reference Notes

• [1.1] [#Diabetes Type 2] 
  - Among obese individuals with at least 1 comorbidity the production of indole, IPA, indole 3-acetic acid, and indole 3-carboxaldehyde is decreased versus lean individuals, suggesting that a change in meta-organismal tryptophan metabolism may occur prior to T2DM onset and thus may contribute to its development.
• [1.2] [#Indole-3-propionic acid, #Tryptophan] 
  - TRP > utilized by the intestinal flora in the intestinal tract and metabolized into ligand molecules indole, indole propionic acid, indole acetic acid, #Skatole, and #Tryptamine > action on of aryl hydrocarbon receptor (AHR).
• [1.3] [#Chronic Obstructive Pulmonary Disease] 
  - In Neutrophil-predominant COPD altered #Tryptophan metabolism in airway #Lactobacilli is associated with reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host interleukin-22 signalling and epithelial cell apoptosis pathways. - airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema and lung function decline, via macrophage–epithelial cell cross-talk mediated by interleukin-22. - Intranasal inoculation of two airway #Lactobacilli restored IAA and recapitulated its protective effects in mice.
• [1.4] [#Indole-3-acetamide (IAM), #Indole-3-aldehyde (I3A) (IAID), #Indole-3-lactic acid, #Indole-3-propionic acid, #Indole-3-pyruvic acid (IPyA), #Indoleacrylic acid (IA)] 
  - 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
• [#Inflamatory bowel disease] - IBD patients have reduced fecal concentrations of the AhR agonist IAA.
• [1.5] [#Pancreatic Cancer] 
  Pancreatic ductal adenocarcinoma (PDAC) > chemotherapy > microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. - Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. - In humans > a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. - Pancreatic ductal adenocarcinoma (PDAC) > #Bacteroides fragilis and #Bacteroides thetaiotaomicron produced 3-IAA in vitro were increased in Responder patients.
• [1.6] [#Indole-3-propionic acid] 
  - The GM metabolism of #Tryptophan also leads to the production of six neuroactive compounds altogether called TRYP-6 affecting the Gut-Brain Axis (GBA). - These six metabolites include indole-3-acetic acid, quinolinate, #kynurenine, indole, #Tryptamine and indole propionic acid
• [1.7] [#Pyruvic acids] 
  - #AHR, especially in barrier tissues of the respiratory and gastrointestinal, can also be activated by dietary and microbial indole-derived metabolites such as pyruvic acid (IPyA), indole acetic acid (IAA), #Indoxyl-3-sulfate, #Indole-3-carbinole (I3C), and 3,3′-di-indolylmethane (DIM).

References Notes