Introduction

The essential amino acid tryptophan is converted to indole by intestinal bacterial cleavage of the tryptophan side chain. After absorption, indole is converted to 3-hydroxy indole (indoxyl or indican) in the liver, where it is conjugated with potassium sulfate or glucuronic acid. It is then transported by the blood to the kidneys for excretion. Increased urinary excretion of indican can be an indicator of gastrointestinal bacterial overgrowth and dysbiosis.

Clinical Application

Because most of the endogenous indoles have a side chain that prevents cleavage and are instead metabolized to skatole, the production of indicans (indoxyl potassium sulfate and indoxyl glucuronate) reflects bacterial activity in the small and large intestines. Box 30-1 lists conditions in which increased levels are found.^1–4 Elevations of indicans are considered an indicator of gastrointestinal dysfunction and overgrowth of anaerobic bacteria (dysbiosis). The indican test can be used to monitor the efficacy of treatment of gastrointestinal dysbiosis.

Interpretation

A positive result may indicate one of several underlying disorders, any of which can lead to bacterial dysbiosis and/or overgrowth, including hypochlorhydria, maldigestion, pancreatic insufficiency, malabsorption of protein, and excessive dietary protein intake (see Box 30-1). Occasionally a positive test can be caused by increased dietary protein prior to testing, which can be prevented by the institution of a moderate protein diet for 2 days before testing.

False-negative results occur when formalin, methenamine, or sulfasalazine (Azulfidine) is present.² Indigo red may occasionally form from slow oxidation. The presence of iodine, salicyluric acid, methylene blue, or thymol causes a violet color that can be removed with the addition of a crystal of sodium thiosulfate. Bile pigments can interfere with the reaction, but can be removed by shaking the urine with barium chloride and filtering.

Conclusion

This simple in-office diagnostic test can be used to determine gastrointestinal dysfunction or dysbiosis. A positive test can indicate the need for additional testing for gastrointestinal pathogens or altered GI function. The test for urine indicant can be a clinically useful tool for identifying and treating dysbiosis and optimizing GI health. A limitation of this test arises from the caustic nature of the test reagents, which require a hood to exhaust fumes and care to avoid skin contact.