Wutzke K D, Heine W E, Plath C, Leitzmann P, Radke M, Mohr C, Richter I, Gülzow H U, Hobusch D
Children's Hospital, Department of Medicine, University of Rostock, Germany.
Eur J Clin Nutr. 1997 Jan;51(1):11-9. doi: 10.1038/sj.ejcn.1600353.
The lactulose H2-breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[13C, 15N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H2-breath test. Additionally the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU (13CO2, [15N]urea, and 15NH3) were investigated.
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. 13C-enrichment in breath as well as 15N-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.
The comparison of the lactose-[13C]ureide 13CO2-breath test and the lactulose H2-breath test showed that the mean increase of the 13C-enrichment in CO2 occurred 1.18 h later than the mean increase of H2 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 BRs were 9.63 +/- 3.4 and 6.07 +/- 1.7 h (P < 0.01), respectively. The 15N-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 15N- and 13C-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 13C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%).
The use of the lactulose H2-breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[13C]ureide 13CO2-breath test in healthy adults. The most important limitations of the lactulose H2-breath test are its low specificity and sensitivity due to dose-dependent accelerations of OCTT, interfering H2-rise from malabsorbed dietary fibre and H2-non-producers. In contrast, our lactose-[13C]ureide 13CO2-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 H2-tests lead to insufficient results.
乳果糖氢呼气试验是评估口盲肠转运时间（OCTT）最广泛使用的非侵入性方法。在本研究中，合成了双标记乳糖 - [13C, 15N]脲（DLLU），以与传统的乳果糖氢呼气试验比较来研究OCTT。此外，还研究了DLLU裂解产物（13CO2、[15N]尿素和15NH3）的细菌分解率（BBR）、消除率和代谢途径。
在第一项研究中，对12名健康成年志愿者早餐后给予DLLU进行单次口服脉冲标记（剂量：1克），在研究前一天，分别在未服用和服用5克未标记乳糖脲（LU）预处理后进行。在一天的时间内，分别以1小时和2小时的间隔收集呼气和尿液。通过连续流动同位素比率质谱法（CF - IRMS）测量呼气中的13C富集以及尿液组分中的15N富集。在第二项研究中，对相同的受试者给予乳果糖（剂量：10克）。在10小时内，分别以一刻钟、半小时和1小时的间隔收集呼气。使用电化学检测器分析呼气中的氢气浓度。
乳糖 - [13C]脲13CO2呼气试验与乳果糖氢呼气试验的比较表明，CO2中13C富集的平均增加比呼气中H2的平均增加晚1.18小时。由两种方法得出的OCTT分别为3.02±1.4小时和1.84±0.5小时（P < 0.05），相应的BRs分别为9.63±3.4小时和6.07±1.7小时（P < 0.01）。在给予DLLU后两到三小时开始，未用LU预处理和用LU预处理后尿液中尿素和氨的15N富集情况。15N和13C示踪剂的累积尿排泄百分比分别为29.9%和13.6%，用LU预处理后略有增加，分别为给药剂量的32.1%和14.6%。发现总共35.2%的13C被呼出，用LU预处理后保持大致恒定（36.2%）。
与乳糖 - [13C]脲13CO2呼气试验相比，在健康成年人中使用乳果糖氢呼气试验评估OCTT在统计学上显著缩短了1.18小时。乳果糖氢呼气试验最重要的局限性是由于OCTT的剂量依赖性加速、来自吸收不良膳食纤维的干扰性H2升高以及非H2产生者，其特异性和敏感性较低。相比之下，我们的乳糖 - [13C]脲13CO2呼气试验被证实可避免这些缺点并产生可靠结果。特别是在需要更高的敏感性和特异性、有IRMS技术可用且乳果糖氢试验结果不足时，推荐使用此试验。
