¹³C mannitol as a novel biomarker for measurement of intestinal permeability

Background: Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of ¹²Carbon (¹²C, regular) mannitol in food or from other sources may interfere with the test's interpretation. ¹³Carbon (¹³C) constitutes 1% of carbon in nature and ¹³C mannitol is a stable isotope. Our aim was to determine the performance of ¹³C mannitol for measurement of intestinal permeability. Methods: Ten healthy volunteers underwent intestinal permeability assay using coadministered ¹²C mannitol, ¹³C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography–mass spectrometry. Key results: We found that ¹³C mannitol can be distinguishable from ¹²C mannitol on tandem mass spectrometry. In addition, ¹³C mannitol had ~20-fold lower baseline contamination compared to ¹²C mannitol. We describe here the ¹³C mannitol assay method for the measurement of intestinal permeability. Conclusions & Inferences: In conclusion, ¹³C mannitol is superior to ¹²C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period.