Microbiota-derived tryptophan metabolites

What is measured?

3-Indoxyl sulfate (3IS), indole-3-acetamide (IAM), indole-3-acetate (IAA), indole-3-aldehyde (IAld), indole-3-lactate (ILA) and indole-3-propionate (IPA).
Method(s): LC-MS/MS (1).

Tryptophan metabolites of the indole pathway

About 5 % of tryptophan is catabolized by the gut microbome, generating so-called microbiome-derived tryptophan metabolites, which include indole (IND), 3-indoxyl sulfate (3IS), and indole derivatives, such as indole-3-acetamide (IAM), indole-3-acetate (IAA), indole-3-acetaldehyde (IAAld), indole-3-aldehyde (IAld), indole-3-acrylate (IacA) and indole-3-propionate (IPA).
Microbiome-derived tryptophan metabolites have diverse biological roles affecting health (Figure 1). Some are ligands of the aryl hydrocarbon receptor (AhR) thereby modulating the immune response, others have anti-inflammatory and anti-oxidative effects, enhance the intestinal epithelial barrier, increase secretion of gut hormones and stimulate intestinal motility. Indoles are generally thought to mediate beneficial health effects, with the exception of 3IS, a host-microbial co-metabolite generated from indole in the liver; 3IS is toxic at high concentrations and associated with vascular disease and renal dysfunction. 3IS is considered as uremic toxin, which is highly (90 %) bound to albumin, and therefore accumulates despite regular hemodialysis (2).


Profiling of microbiota-derived metabolites.

Specimen, collection and processing

Volume: Minimum volume is 60 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Samples should be put on ice immediately after collection and stored at -80 °C.


Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 3IS: 0.9-30 µmol/L; IAM: 0-10 nmol/L; IAA: 0.3-23 µmol/L; IAld: 0.01-0.20 µmol/L; ILA: 0.08-5 µmol/L; IPA: 0.5-12 µmol/L.
Intraclass correlation coefficient (ICC): na.


1. Midttun, O., Hustad, S., and Ueland, P.M. (2009). Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Sp 23, 1371-79.
2. Roager, H. M., & Licht, T. R. (2018). Microbial tryptophan catabolites in health and disease. Nat Commun, 9, 3294.

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