Indoxyl glucoside (indican) is an indole compound that is formed through gut microbial metabolism from dietary tryptophan and a sulfation reaction in liver hepatic cells. After being transported into gut microbes, tryptophan undergoes a reaction with the enzyme tryptophanase to form indole. Indole that is produced from the gut microbes then enters systemic circulation. Following this absorption, indole is transported to the liver where it forms 3-hydroxyindole (indoxyl or indican) in a reaction catalysed by the cytochrome P450 2E1 enzyme. Indican, when oxidized, turns blue. Ultimately this compound undergoes sulfation or glucuronidation as a normal xenobiotic metabolite before being excreted by the kidneys. It is a uremic toxin as identified by the European Uremic Toxin Working Group and accumulates in the presence of Lactobacillus bacteria in the gut. It is found in individuals affected by the blue diaper syndrome (a rare, autosomal recessive metabolic disorder characterized in infants by bluish urine-stained diapers), the patients exhibit a defect in tryptophan metabolism, leading to an increase in indican synthesis. Indican is then excreted into the urine and from there into the diaper where, upon exposure to air, it is converted to indigo blue dye due to oxidation by atmospheric oxygen. An increased urinary excretion of indican is seen in Hartnup disease from the bacterial degradation of unabsorbed tryptophan. Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan), which leads to excessive bacterial fermentation of tryptophan (to indole) in the gut. It exerts toxic effects when it forms indoxyl sulfate. As such, it reduces Erythropoetin production which ultimately results in renal anemia. It is also shown to cause vascular calcification and disrupt the electron transport chain and oxidative phosphorylation causing muscle atrophy.

Metabolism and Physiological Effects of Indoxyl glucoside (indican) References