3-Indoleacetate

Urine
Optimal Result: 0.46 - 9.21 ug/mg creatinine.

Indoleacetic acid (IAA), or indole-3-acetate, is produced by the bacterial fermentation of the amino acid tryptophan.

IAA can be formed from several common gut microbes such as Clostridia species, Escherichia coli, and Saccharomyces species.

Common Dietary Sources:

High tryptophan intake, green/black tea

References:

- Blaut M, Clavel T. Metabolic Diversity of the Intestinal Microbiota: Implications for Health and Disease. J Nutr. 2007;137(3):751S-755S.

- Russell WR, Duncan SH, Scobbie L, et al. Major phenylpropanoidderived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013;57(3):523-535.

- Rao RP, Hunter A, Kashpur O, Normanly J. Aberrant synthesis of indole-3-acetic acid in Saccharomyces cerevisiae triggers morphogenic transition, a virulence trait of pathogenic fungi. Genetics. 2010;185(1):211-220.

- Evenepoel P, Meijers BKI, Bammens BRM, Verbeke K. Uremic toxins originating from colonic microbial metabolism. Kidney Int.76:S12-S19.

- Karu N, McKercher C, Nichols DS, et al. Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study. BMC Nephrol. 2016;17(1):171.

- Sallée M, Dou L, Cerini C, Poitevin S, Brunet P, Burtey S. The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease. Toxins. 2014;6(3):934-949.

- Gevi F, Zolla L, Gabriele S, Persico AM. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism. Mol Autism. 2016;7:47.

- Wong PW, Lambert AM, Pillai PM, Jones PM. Observations on nicotinic acid therapy in Hartnup disease. Arch Dis Child. 1967;42(226):642-646.

What does it mean if your 3-Indoleacetate result is too low?

Low levels of 3-indoleacetate may occur if the patient is on a low-protein diet or gastrointestinal disorders are present. 3-indoleacetate may be produced from the body’s tryptophan metabolism or via tryptophan metabolism by the gut bacteria in the microbiome.

3-indoleacetate may participate in gut-microbiome crosstalk to promote tolerance and regulatory T-cell production. A loss of diversity in the gut microbiome may occur due to antibiotic use or due to chronic psychological stress (insufficiency dysbiosis). The presence of inflammatory bowel disease (IBD) may decrease 3-indoleacetate levels. Exposure to rotenone or similar pesticides may also decrease levels.

If indicated, consider supporting 3-indoleacetate synthesis with tryptophan and vitamin B3. Both 5-hydroxyindoleacetate and 3-indoleacetate may be low if the diet is low in tryptophan. Giving tryptophan separately between meals may improve absorption.

NOTE: Tryptophan or 5-hydroxytryptophan (5-HTP) supplementation is contraindicated in patients using serotonin-reuptake inhibitor medications (SSRIs). Check all medication use with a medical professional.

What does it mean if your 3-Indoleacetate result is too high?

High levels of 3-indoleacetate may occur if the patient is on a high-protein diet, or if tryptophan or 5-HTP supplements are being used. The presence of digestive disorders can leave large amounts of undigested protein in the gut lumen and may also increase levels. The presence of liver or kidney disorders may also increase circulating levels of 3-indoleacetate, with can induce endothelial dysfunction, inflammation, and oxidative stress. Drinking coconut water, which naturally contains 3-indolacetate, may artificially increase levels.

- If amino acid supplements are being used that contain phenylalanine (as well as or instead of tryptophan) are in use, that may also increase levels of 3-indolacetate.

- If the levels of both 2-hydroxyphenylacetate and 3-indoleacetate are high, there may be an inherited low-activity enzyme preventing the proper breakdown of phenylalanine.

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