Gastrointestinal handling of glycosyl [13C]ureides

Morrison, Douglas J.; Dodson, Brian; Preston, Thomas C.; Weaver, Lawrence T.

doi:10.1038/sj.ejcn.1601637

Cited by 25 publications

(30 citation statements)

References 31 publications

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“…In the last decade, breath tests with 13 C-labelled glycosyl ureides for measuring the OCTT have been established worldwide (Heine et al, 1995;Ruemmele et al, 1997;Wutzke et al, 1997;Morrison et al, 1998Morrison et al, , 1999Morrison et al, , 2003Geypens et al, 1999;Jackson et al, 1999;van den Driessche et al, 2000;Christian et al, 2002). Furthermore, 15 N-labelled LU has been used for studying colonic nitrogen metabolism as a biomarker to assess the effects of pro-and pre-biotics on the intestinal flora in humans, and for measuring the transfer of 15 N (de Preter et al, 2004;Jackson et al, 2004;Geboes et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to several papers published earlier dealing with the evaluation of OCTTs, a reduced and cheaper pre-dosing protocol with merely 5 Â 100 mg LU has been applied in this study. Higher dosages of up to 5 Â 1 g LU have been used in adults so far (Morrison et al, 2003;Wutzke and Glasenapp, 2004). It could be demonstrated that the application of 500 mg 13 C-LU and the pre-dosing with 5 Â 100 mg LU are high enough to induce the enzyme activity and to give reliable results.…”

Section: Discussionmentioning

confidence: 99%

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The duration of enzyme induction in orocaecal transit time measurements

Wutzke

Schutt

2007

Eur J Clin Nutr

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Objective: In this study, the duration of enzyme induction provoked by unlabelled lactose ureide (LU) in orocaecal transit time (OCTT) measurements with lactose-[ 13 C]ureide ( 13 C-LU) was evaluated. Design: Experimental study. Setting: University of Rostock, Children's Hospital, Research Laboratory. Subjects: Fifteen healthy adults aged 19-54 years. Intervention: One-half gram of 13 C-LU was administered together with a continental breakfast. After 1 week, the test was repeated after pre-dosing of 5 Â 100 mg LU on the day before the study began. The 13 C-LU ingestion was repeated under identical conditions but without pre-dosing 1 and 3 weeks after pre-dosing. Expired air samples were taken over 14 h. 13 CO 2 -enrichment was measured by isotope ratio mass spectrometry (SerCon, Crewe, UK). The OCTT was calculated from the interval between 13 C-LU administration and the detection of a significant and sustained 13 C-rise of 2 delta over baseline in breath. Results: Without pre-dosing, an OCTT of 419782 min was measured. The pre-dosing resulted in higher 13 C-enrichments and caused a significant OCTT shortening of 311799 min (P ¼ 0.028). One and 3 weeks after pre-dosing, the measured OCTT again increased to 4047124 and 3797103 min, respectively. Conclusions: Pre-dosing with LU before pulse labelling with 13 C-LU led to an induction of enzyme activity and resulted in a definitive estimation of the OCTT when using a threshold of 2 delta over baseline. After 1 and 3 weeks, respectively, the OCTT was no longer significantly different to those without pre-dosing, indicating the disappearance of enzyme induction. Therefore, a pre-dosing with LU on the day before 13 C-LU ingestion is essential for OCTT measurements.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The duration of enzyme induction in orocaecal transit time measurements

Wutzke

Schutt

2007

Eur J Clin Nutr

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“…Furthermore, it could be demonstrated that pre-dosing with merely 3 Â 120 mg GU as well as the equimolar dosage of 3 Â 200 mg CU is high enough to induce the enzyme activity and to give reliable results. In previously published papers, higher dosages of up to 5 Â 1 g LU have been used in adults (Morrison et al, 2003;Wutzke and Glasenapp, 2004). The relatively low dosage of GU and CU, respectively, applied in this study minimize a potential influence of pre-dosing on OCTT.…”

Section: Discussionmentioning

confidence: 99%

“…Since the primary publication in 1995, 13 CO 2 -breath tests for measuring the OCTT preferentially by using 13 C-LU have become generally accepted worldwide (Heine et al, 1995;Ruemmele et al, 1997;Geypens et al, 1999;Jackson et al, 1999;Van den Driessche et al, 2000;Christian et al, 2002;Morrison et al, 1998Morrison et al, , 1999Morrison et al, , 2003Wutzke and Sattinger, 2006;Schneider et al, 2007;Berthold et al, 2009). It is commonly assumed that 13 C-GU and the corresponding glucose ureide hydrolase are the key substance and the key enzyme, respectively, of the enzymatic sugar ureide degradation process that is exclusively initiated by C. innocuum in the human caecum (Mohr et al, 1999;Wutzke and Glasenapp, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a pre-treatment with LU on the day before 13 C-LU ingestion is essential for OCTT measurements. However, Morrison et al (2003) described the pre-dosing with GU before 13 C-LU ingestion but without measuring the faecal 13 C-excretion. In recently published papers, assessing the effects of pro-and prebiotics on the intestinal ammonia metabolism in humans when using lactose-[ 15 N 2 ]ureide ( 15 N-LU) as biomarker, the faecal 15 N-excretion has been investigated (De Preter et al, 2004;Jackson et al, 2004;Geboes et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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

Wutzke

Mix

2010

Eur J Clin Nutr

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Background: To date, the measurement of the orocaecal transit time (OCTT) with lactose-[ 13 C]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-[ 13 C, 15 N]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 Â 120 mg glucose ureide (GU) and 3 Â 200 mg cellobiose ureide (CU), respectively, on the day before study begin. The 13 C-and 15 N-enrichments were measured by isotope ratio mass spectrometry. The OCTT was calculated by the detection of a significant 13 CO 2 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 ¼ 0.033) or CU pre-dosing (6.0±2.2 h, P ¼ 0.039). The respective renal 13 C-and 15 N-excretions amounted to 24.5 and 45.6, 24.7 and 54.0, and 22.5 and 50.1%, respectively, whereas the faecal 13 C-and 15 N-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-[ 13 C]ureide is the matrix of the bacterial degradation in the caecum.

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Advantages of deuterium‐labelled mixed triacylglycerol in studies of intraluminal fat digestion

Slater

Preston

Weaver

2005

Rapid Comm Mass Spectrometry

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The 13 C-mixed triacylglcerol (MTG,1, C]octanoyl glycerol) breath test is a noninvasive measure of intraluminal fat digestion. Recovery of 13 C in breath CO 2 is incomplete (<50%) owing to sequestration of 13 C into organic molecules via the tricarboxylic acid (TCA) cycle. In addition lack of knowledge of CO 2 production rate (VCO 2 ) during the test leads to errors in the calculated percentage dose recovered (PDR). 2H sequestration into organic molecules is low ($4%) and is not influenced by factors that affect VCO 2 such as food intake or physical activity. After oxidation of 2 H-labelled macromolecules, the label appears in body water, which can be sampled O was calculated from the plateau enrichment, which was reached by 6 h in both saliva and urine. Recovery of 2 H calculated using measured TBW was compared with that using an estimated value of TBW. Mean recovery of 2 H in saliva was 99.3% and in urine was 96.4%. Errors introduced by estimating TBW were <5%. 1 -10 13 C-breath tests are particularly attractive for use in children because they are non-invasive, and pose no radiation hazard. A problem with many 13 C-breath tests is that recovery of 13 C in breath CO 2 is less than 50%, even in healthy subjects, owing to the sequestration of label into organic compounds via acetylCoA and the tricarboxylic acid (TCA) cycle. 3,11 -16 Quantitation of tracer recovery requires knowledge of carbon dioxide production rate (VCO 2 ) because labelled CO 2 originating from oxidation of the tracer is diluted by endogenously produced CO 2 from metabolism. A resting value of VCO 2 based on basal metabolic rate is often assumed, 11,14 but, even if resting VCO 2 is measured, 17,18 this may not be appropriate because subjects, especially children, rarely remain at rest for the duration of the test, which typically lasts for about 6 h. VCO 2 is increased during physical activity and after food intake; therefore, use of resting VCO 2 will underestimate the true CO 2 production rate resulting in an underestimation of the quantity of tracer recovered. 16,19 Another confounding factor for 13 C-breath tests is the natural abundance variation in the usual diet, 20,21 resulting in the need for subjects to eat a diet containing ingredients of low 13 C abundance, possibly for several days before the test and during the test. The mixed triacylglycerol (MTG) breath test was developed as an indirect measure of intraluminal fat digestion in adults with impaired pancreatic function.9,22 The 13 C [MTG] breath test has been used to assess the need for pancreatic enzyme replacement therapy in children with cystic fibrosis and to assess the ideal dose, 3,8 but it has not been widely adopted because it lacks specificity, 23 and requires frequent breath sampling over a period of 5-6 h. [1-13 C]octanoate, which is absorbed and reaches the liver via the portal vein. Less than 5% ingested 13 C is excreted in

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Gastrointestinal handling of glycosyl [13C]ureides

Cited by 25 publications

References 31 publications

The duration of enzyme induction in orocaecal transit time measurements

The duration of enzyme induction in orocaecal transit time measurements

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

Advantages of deuterium‐labelled mixed triacylglycerol in studies of intraluminal fat digestion

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