The metabolic fate of doubly labelled lactose-[13C, 15N]ureide after pre-dosing with different ureides

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Background:To date, the measurement of the orocaecal transit time (OCTT) with lactose-[13C]ureide usually requires a pre-dosing with the analogous substrate in its unlabelled form.Objective:In this study, the enzyme induction provoked by different unlabelled sugar ureides in OCTT measurements when using doubly labelled lactose-[13C, 15N]ureide (DLLU) was evaluated.Methods:Thirteen healthy adults (age: 22–58 years) received 500 mg DLLU together with a standardized breakfast. Expired air, urine and faeces were collected over a period of 14, 48 and 72 h, respectively. After 1 and 2 weeks, the test was repeated after pre-dosing of 3 × 120 mg glucose ureide (GU) and 3× 200 mg cellobiose ureide (CU), respectively, on the day before study begin. The 13C- and 15N-enrichments were measured by isotope ratio mass spectrometry. The OCTT was calculated by the detection of a significant 13CO2 increase.Results:In comparison with the period without pre-dosing (7.8±2.2 h), the measured OCTT was significantly lowered either after GU pre-dosing (5.8±1.9 h, P=0.033) or CU pre-dosing (6.0±2.2 h, P=0.039). The respective renal 13C- and 15N-excretions amounted to 24.5 and 45.6, 24.7 and 54.0, and 22.5 and 50.1%, respectively, whereas the faecal 13C- and 15N-excretions amounted to 12.1 and 45.8, 4.8 and 21.5, and 9.6 and 39.8%, respectively.Conclusions:Pre-dosing with unlabelled GU and CU before the administration of DLLU led to an unequivocal induction of the enzyme activity and resulted in a definitive estimation of the OCTT, clearly demonstrating that glucose-[13C]ureide is the matrix of the bacterial degradation in the caecum.

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