Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls

Abstract

Mucosal barrier dysfunction contributes to gastrointestinal diseases. Our aims were to validate urine sugar excretion as an in vivo test of small bowel (SB) and colonic permeability and to compare permeability in patients with irritable bowel syndrome-diarrhea (IBS-D) to positive and negative controls. Oral lactulose (L) and mannitol (M) were administered with (99m)Tc-oral solution, (111)In-oral delayed-release capsule, or directly into the ascending colon (only in healthy controls). We compared L and M excretion in urine collections at specific times in 12 patients with IBS-D, 12 healthy controls, and 10 patients with inactive or treated ulcerative or microscopic colitis (UC/MC). Sugars were measured by high-performance liquid chromatography-tandem mass spectrometry. Primary endpoints were cumulative 0-2-h, 2-8-h, and 8-24-h urinary sugars. Radioisotopes in the colon at 2 h and 8 h were measured by scintigraphy. Kruskal-Wallis and Wilcoxon tests were used to assess the overall and pairwise associations, respectively, between group and urinary sugars. The liquid in the colon at 2 h and 8 h was as follows: health, 62 ± 9% and 89 ± 3%; IBS-D, 56 ± 11% and 90 ± 3%; and UC/MC, 35 ± 8% and 78 ± 6%, respectively. Liquid formulation was associated with higher M excretion compared with capsule formulation at 0-2 h (health P = 0.049; IBS-D P < 0.001) but not during 8-24 h. UC/MC was associated with increased urine L and M excretion compared with health (but not to IBS-D) at 8-24 h, not at 0-2 h. There were significant differences between IBS-D and health in urine M excretion at 0-2 h and 2-8 h and L excretion at 8-24 h. Urine sugars at 0-2 h and 8-24 h reflect SB and colonic permeability, respectively. IBS-D is associated with increased SB and colonic mucosal permeability.

Crosstalk at the mucosal border: importance of the gut microenvironment in IBS

“…Apart from this last line of defence, the mucus layer covering the intestinal mucosa as well as the gut microbiota and products from the immune system (such as defensins and secreted antibodies) have important roles in maintaining gut integrity. 135 Between 12% and 50% of patients with IBS have been reported to have altered intestinal permeability in research studies 136 using various methods to reflect gut permeability at different parts of the gastrointestinal tract, [137][138][139] and both postinfectious IBS as well as nonselected groups of patients with IBS have been investigated. An acute bacterial infection results in a transient increase in intestinal permeability.…”

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate

“…There may be interfering substances that could affect the assayed levels of sugars, particularly food derived substances. Gut transit of liquids can also be a problem as a liquid bolus can reach the colon within 2 hours, meaning that collection of urine 5 hours post sugar dosing may reflect colonic absorption [Rao et al 2011].…”

Intestinal barrier: A gentlemen’s agreement between microbiota and immunity

“…When actin contracts, it leads to increased permeability to electrolytes and small molecules [105] . In the context of inflammatory bowel syndrome (IBS), some studies have shown that the intestinal barrier is compromised, and decreased expression and differential distribution of tight-junction proteins are observed [106][107][108][109][110] . The nature of the luminal or mucosal factors that affect the function of tight junction proteins is still unclear.…”