Standardising the lactulose mannitol test of gut permeability to minimise error and promote comparability.

Simon Patrick Hogan,Ivana R Sequeira,Roger D Hurst,Marlena C Kruger,Roger G Lentle

doi:10.1371/journal.pone.0099256

Simon Patrick Hogan, Ivana R Sequeira + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0099256

Copy DOI

Journal: PloS one	Publication Date: Jun 5, 2014
Citations: 139	License type: CC BY 4.0

Affiliation: Massey University, Plant & Food Research

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.

Highlights

The 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 2K-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
A number of tests based on the passive absorption of simple sugars have been used to assess gut permeability as an index of recovery from inflammatory bowel disease (IBD) [1,2] and from autoimmune diseases such as coeliac disease [3,4] The ratio of the quantities of urinary lactulose and mannitol excreted during a given period has been used most frequently [5,6], a number of workers have used rhamnose rather than mannitol [7,8]

Summary

Introduction

A number of tests based on the passive absorption of simple sugars have been used to assess gut permeability as an index of recovery from inflammatory bowel disease (IBD) [1,2] and from autoimmune diseases such as coeliac disease [3,4] The ratio of the quantities of urinary lactulose and mannitol excreted during a given period has been used most frequently [5,6], a number of workers have used rhamnose rather than mannitol [7,8]. The early peak in mannitol excretion causes the LMR to be lower when cumulative excretion is assessed over 2 hours whilst the later peak in lactulose excretion and lower rate of mannitol excretion 4 hours after dosage will cause the LMR to increase when cumulative excretion is assessed over 4 or more hours [13] These effects may be magnified in the presence of a pro-inflammatory condition [16,17,18] or a proinflammatory stimulus such as a single 600 mg dose of aspirin [19,20] as these will cause the overall excretion of lactulose to increase [4,21] and that of mannitol to be reduced [13]. We determined the optimal sampling period and related this to intestinal residence

Objectives

Methods

Results

Conclusion