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

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 99mTc-oral solution, 111In-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.

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Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821993586 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199358

Author(s):

Nikita Hanning ◽

Adam L. Edwinson ◽

Hannah Ceuleers ◽

Stephanie A. Peters ◽

Joris G. De Man ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Barrier Function ◽

Significant Proportion ◽

Healthy Controls ◽

Barrier Dysfunction ◽

Irritable Bowel

Background and Aim: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. Methods: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. Results: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17–50%), IBS-D (37–62%) and IBS-C (4–25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). Conclusions: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.

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Excess nitric oxide does not cause cellular, vascular, or mucosal dysfunction in the cat small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.1.g34 ◽

1995 ◽

Vol 269 (1) ◽

pp. G34-G41 ◽

Cited By ~ 2

Author(s):

P. Kubes ◽

P. H. Reinhardt ◽

D. Payne ◽

R. C. Woodman

Keyword(s):

Nitric Oxide ◽

Cell Injury ◽

Venous Pressure ◽

Platelet Activating Factor ◽

Cell Permeability ◽

Mucosal Barrier ◽

Barrier Dysfunction ◽

Mucosal Permeability

The overproduction of nitric oxide in the small bowel has been invoked as a cytotoxic event in the vascular, mucosal, and whole organ dysfunction associated with inflammation. We assessed whether exogenous administration of nitric oxide in the form of nitric oxide donors (CAS 754, SIN-1) could cause microvascular and mucosal barrier dysfunction in vivo or epithelial and endothelial cell permeability alterations and cell injury in vitro. Increasing concentrations of CAS 754 or SIN-1 were infused locally into autoperfused segments of cat ileum at 30-min intervals. Baseline epithelial permeability (blood-to-lumen clearance of 51Cr-EDTA) was not affected by CAS 754, whereas vascular protein clearance was reduced. The latter effect could almost entirely be explained by a decrease in intestinal capillary hydrostatic pressure. Therefore, in some experiments venous pressure was elevated and the microvascular reflection coefficient for total proteins was estimated at filtration-independent rates. This direct measurement of microvascular permeability was unaffected by exogenous nitric oxide. CAS 754 did not increase permeability across monolayers of endothelial or epithelial cells and did not cause cell injury. Next, we assessed the possibility that excess nitric oxide may be detrimental, but only in inflamed intestine, by infusing CAS 754 with platelet-activating factor; the latter directly increases microvascular and mucosal permeability. CAS 754 did not exacerbate but rather reduced platelet-activating factor-induced rise in microvascular and mucosal permeability. These results suggest that high concentrations of nitric oxide do not cause breakdown of mucosal or microvascular barrier integrity under normal or inflammatory conditions.

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