Effects of pre- and post-absorptive factors on the lactulose/rhamnose gut permeability test

Abstract

A B S T R A C TIt is assumed that the outcome of the lactulose/rhamnose gut permeability test is not influenced by pre-or post-absorptive factors. The aim of our study was to investigate the role of a preabsorptive factor, i.e. small-intestinal transit, and a post-absorptive factor, i.e. renal clearance. Ten healthy male subjects were studied. Urinary lactulose and rhamnose excretion was measured after intraduodenal administration of lactulose and rhamnose following induction of increased intestinal permeability using chenodeoxycholic acid (chenodiol), in the absence and in the presence of accelerated intestinal transit. Urinary sugar excretion was measured after intravenous administration of either a regular dose (50 mg/50 mg) or a high dose (250 mg/250 mg) of lactulose/rhamnose. The intraduodenal experiments showed that a combination of accelerated small-bowel transit and increased permeability did not lead to significant differences in the recovery of lactulose (P l 0.647) or rhamnose (P l 0.889), or in the lactulose/rhamnose ratio, compared with those under conditions of increased permeability alone (P l 0.68). However, lactulose recovery was significantly lower (P l 0.025) after intravenous administration of a high dose of the sugars. There was no significant difference in urinary rhamnose recovery (P l 0.575) between the high and the regular doses. This resulted in a significantly lower lactulose/rhamnose ratio (P l 0.021) after intravenous administration of a high dose, compared with a regular dose, of the sugars. In conclusion, the assumption that post-absorptive processes do not influence the outcome of the lactulose/rhamnose permeability test appears not to be valid.

Does fluid loading influence measurements of intestinal permeability?

“…Nevertheless, we found a similar recovery rate of lactulose, rhamnose, and 3-OMG within a comparable urine collection period (5 hours versus 6 hours). In our study, the L/R ratio is also comparable with the ratios from other studies in healthy subjects [6,11,12]. …”

“…It has been shown in volunteers that renal clearance of lactulose but not of rhamnose is dependent on the intravenously administered quantity of the respective sugar [12]: urinary lactulose recovery was significantly lower after intravenous administration of a high dose in comparison with the regular dose. Although lactulose cannot enter the cells and therefore has an extracellular distribution, the monosaccharides might be present both intracellularly and extracellularly.…”

Homeostasis of the gut barrier and potential biomarkers

“…Recently, renal clearance of rhamnose but not lactulose was shown not to depend on the quantity of these sugars in the circulation (67). Thus, a relative increase in permeation of lactulose and rhamnose in the small intestine may be underestimated in this test (267a). …”

Measurement of the intestinal permeability in chronic kidney disease

“…In conclusion, literature results on the recovery of both sugars are conflicting [30,32] . Differences in administration methods and dosage might be an explanation.…”

“…The percentage of the substance excreted in urine is defined as the urinary recovery and is often expressed as the ratio of the recovery of the administered sugars. Even though renal clearance of these sugars is assumed to be of little or no influence on the ratio since both sugars are equally affected by a reduced eGFR [17] , van Nieuwenhuizen et al [30] observed different results in their study evaluating the influence of preand postabsorptive factors on the lactulose/rhamnose ratio. The urinary excretion of lactulose and rhamnose was measured in 10 healthy males after intravenous administration of different quantities of each sugars.…”