Evaluation of oro-coecal transit time: A comparison of the lactose-[C-13, N-15]ureide (CO2)-C-13- and the lactulose H-2-breath test in humans

Objective: The lactulose H-2-breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[C-13, N-15]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H-2-breath test. Additionally, the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU ((CO2)-C-13, [N-15]urea, and (NH3)-N-15) were investigated. Design and subjects: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hour-intervals, respectively, over a one-day period. C-13-enrichment in breath as well as N-15-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector. Results: The comparison of the lactose-[C-13]ureide (CO2)-C-13-breath test and the lactulose H-2-breath test showed that the mean increase of the C-13-enrichment in CO2 occurred 1.18 h later than the mean increase of H-2 in breath. The resulting OCTTs derived from the two methods were 3.02 +/- 1.4 and 1.84 +/- 0.5 h (P < 0.05) and the corresponding BBRs were 9.63 +/- 3.4 and 6.07 +/- 1.7 h (P < 0.01), respectively. The N-15-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLU-administration. The cumulative percentage urinary excretion of the N-15- and C-13-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the C-13 was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%). Conclusions: The use of the lactulose H-2-breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[C-13]ureide (CO2)-C-13-breath test in healthy adults. The most important limitations of the lactulose H-2-breath test are its low specificity and sensitivity due to dose-dependent accelerations of OCTT, interfering H-2-rise from malabsorbed dietary fibre and H-2-non-producers. In contrast, our lactose-[C-13]ureide (CO2)-C-13-breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMS-technique is available and if lactulose H-2-tests lead to insufficient results.