3-Indolepropionic acid (IPA), or indole-3-propionic acid, is a potent neuroprotective antioxidant.
IPA is endogenously produced by human microbiota and detected when the species Clostridium sporogenes is present in the gastrointestinal tract.
C. sporogenes, uses tryptophan to synthesize indole and subsequently IPA, is the only species of bacteria known to synthesize IPA at levels which are subsequently detectable in the blood.
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IPA is a potent scavenger of hydroxyl radicals, more than melatonin, the most potent scavenger of hydroxyl radicals that is synthesized by human enzymes.
Unlike other antioxidants, and similar to melatonin, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.
Levels of IPA in human blood plasma are correlated with a lower risk of type 2 diabetes and higher consumption of fiber-rich foods.
Indole is produced from tryptophan by bacteria that express tryptophanase.
IPA binds to the pregnane X receptor (PXR) in intestinal cells.
This binding , facilitates mucosal homeostasis and barrier function.
Following its intestinal absorption and distribution to the brain, it confers a neuroprotective effect against cerebral ischemia and Alzheimer’s disease.
Lactobacillus species metabolize tryptophan into indole-3-aldehyde (I3A) which acts on intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.
Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells.
Indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.