Measurement of intestinal permeability using lactulose and mannitol with conventional five hours and shortened two hours urine collection by two different methods: HPAE-PAD and LC-MSMS

Abstract

Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Usually this test involves a time consuming procedure of about 5 hour’s urine collection, which makes the test incompatible to some extent. As the results are expressed as the ratio of lactulose and mannitol recovered in urine within certain time, it may be possible to get similar result despite the reduced urine collection time of 2 hours. Moreover, different laboratories do the test by different methods, which make the results incomparable between laboratories. Here, we are also trying to find the correlation between results from most commonly used methods: HPAE-PAD and LC-MSMS. The lactulose: mannitol (LM) test was performed in a cohort of Bangladeshi infants considered at-risk for environmental enteropathy. 208 urine specimens from 104 (52 male and 52 female) infants were collected at 2 and 5 hours after LM solution administration and were tested for lactulose and mannitol by two different methods, one HPAE-PAD platform and another LC-MSMS platform. Median age of the children was 15.0 months (range 6.9 to 25.8 months) and their mean weight-for-age z-score was -0.92. A higher percentage of lactulose and mannitol recovery was found in 5 hours urine collection than in the corresponding 2 hours by both HPAE-PAD and LC-MSMS method, but when results were expressed as lactulose to mannitol ratio (LMR) there was no significant difference between 2 and 5 hours urine collection in both HPAE-PAD (P = 0.138) and LC-MSMS (P = 0.099) method. LMR based on 2 hours urine collection correlated well with LMR based on traditional 5 hours urine collection (Spearman’s correlation coefficient 0.578 and 0.604 respectively for HPAE-PAD and LC-MSMS). In future, LM test to assess intestinal permeability in children can be simplified by shortening the urine collection time from 5 hours to 2 hours.

Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet—Results of a Randomized, Placebo-Controlled, Pilot Trial

“…Most of the studies consider the L/M value of 0.03 as a cut-point for intestinal permeability [ 9 , 10 , 41 ]. Other studies use a value of 0.09 as a reference, observed in healthy individuals [ 11 , 42 ]. Therefore, because of these discrepancies, in our study, we adopted a reference value of L/M ratio > 0.08 as an indication of intestinal permeability, following the literature data referring to children with CD [ 8 ].…”

The effect of lactose and a prototype Lactobacillus acidophilus fermentation product on digestibility, nitrogen balance, and intestinal function of weaned pigs1

“…Lactulose and mannitol recoveries (%) were calculated as the amount of these sugars excreted (g/d) in the urine [calculated as total urine weight (g) times lactulose or mannitol concentration (%)] divided by the amount of lactulose or mannitol given (g/d) orally times 100. Lactulose:mannitol ratio was calculated by dividing lactulose recovery by mannitol recovery ( Musa et al, 2019 ).…”

Increased urinary volumes in symptomatic Ménière’s Disease

“…The urinary excretion of two orally administered non-metabolizable sugars, lactulose and mannitol, also known as the “double sugar test” is a well-known, validated, non-invasive method to evaluate the intestinal permeability, because their urinary concentration is an indirect index of their intestinal absorption [10]. The results are expressed as the ratio of lactulose and mannitol recovered in the urine; it is a reliable marker, independent from the etiology of altered intestinal permeability and from the methods of collection [11]. It has been also considered for screening purposes in different clinical conditions, especially in children, in order to avoid more invasive tests, or in the assessment of the responses to new treatments [12].…”