A novel stable isotope breath test: 13C-labeled glycosyl ureides used as noninvasive markers of intestinal transit time.

Abstract

Breath tests are widely used for diagnosis and control of treatment efficacy. There is a need for breath test substrates that reflect intestinal transit times under various conditions. We synthesized a new class of breath test substrates, 13C-labeled glycosyl ureides, which are specific markers for the action of colonic microbial flora. We then investigated their usefulness as markers of intestinal transit time. Bolus ingestion of 1 g lactose or cellobiose 13C-ureide resulted in bacterial cleavage of the N-glycosyl bond and subsequent urea hydrolysis. 13CO2 appeared in breath and was determined by gas-isotope-ratio-mass spectrometry. Label first appeared after 5-6 h, peak excretion occurred between 8-14 h, and the signal returned to baseline after 18-24 h. Metoclopramide (10 mg) administered 1 h before the substrate advanced the onset of the signal by 2.4 +/- 1.95 h (mean +/- SD; n = 7; p < 0.05) and the time of peak response by 0.8 +/- 1.44 h. Loperamide (16 mg) broadened the peak and delayed the time of breath signal onset by 1.0 +/- 2.78 h and peak excretion by 4.0 +/- 3.7 h (p < 0.05). The glycosyl ureide breath test reflected intestinal transit time and rapid changes in gastrointestinal motility. This test should be useful in the diagnosis of a variety of gastrointestinal motility disorders and in the development of drugs that affect gastrointestinal motility.