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Targeted Metabolomics Services

Microbiota-derived tryptophan metabolites

indole-met
Updated 21/12/2022

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).

Indication(s)

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.

Transportation

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: 10-200 nmol/L; ILA: 0.08-5 µmol/L; IPA: 0.5-12 µmol/L.
Intraclass correlation coefficient (ICC): na.

Literature

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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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs

Kynurenines, proteins, ratio-derived metabolites



SCFAs, indoles, choline metabolites, amino acid derived



B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers
65
18
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acids and catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3, DC, C4, C4-OH , C4-DC , iC5 , C5-DC, C5:1 , C6 , C8, C10, C12, C14 , C14-OH, C16, C16-OH, C18 , C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate, Ketone bodies, 3-Hydroxybutyrate, Acetoacetate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: Kynurenine, Kynurenic acid, Quinaldic acid, Anthranilic acid, 3-Hydroxykynurenine, Xanthurenic acid, 3-Hydroxyanthranilic acid, Picolinic acid, Quinolinic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

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SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline ,Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

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B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (ul)
150
100
200
200
Analytical technique
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS
Turnaround time (weeks)
1
1
1
1

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