Standardising the Lactulose Mannitol Test of Gut Permeability to Minimise Error and Promote Comparability

Abstract

BackgroundLactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence.MethodsHalf-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling.Key ResultsThe between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars.ConclusionThe results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large intestine.

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers

“…Based on a prior report [16], LMR was determined using 4-h pooled urine collected from subjects who had fasted for at least 12 h, emptied their bladder, and had orally consumed a sugar solution prepared by dissolving 10 g of lactulose and 5 g of mannitol in 400 mL of water. During the fasting period, subjects were allowed to drink sugar-free water.…”

The complex task of measuring intestinal permeability in basic and clinical science

“…Moreover, there are no standardized protocols, resulting in variations across studies that make comparisons difficult. As several recent studies have suggested, consistency in the probes used, test duration, and fasting times could help reduce variations . Reducing some confounding factors, as in the paper by Grover et al ., provide promising improvements to in vivo techniques …”

The gut reaction to traumatic brain injury

“…Studies of TBI patients show an increase in the ratio of orally ingested lactulose (a marker of paracellular permeability) to mannitol (a marker of transcellular permeability) in urine. 16,17 The lactulose-mannitol test as well as a dye permeability test also shows that injury inflicted exclusively to the brain of rodents by methods such as controlled cortical impact (CCI) is sufficient to increase paracellular permeability. [18][19][20] Furthermore, disruption of the intestinal epithelial barrier following TBI in rodents is accompanied by decreased expression of tight junction proteins Occludin and ZO-1 as well increased expression of MLCK in the intestine, providing additional support for a paracellular mechanism.…”