Our aim was to understand the information from differential two-sugar excretion (2-SE) in measuring intestinal permeability. In a crossover study in 12 healthy volunteers, we compared urinary excretion ratios of lactulose (L) to mannitol [(M) LMR] after ingestion in liquid formulation (LF) or in delayed-release, methacrylate-coated capsules (CAP). Both formulations were radiolabeled. Urine was collected every 2 hours from 0-8h, and from 8-24h. Two hours after LF, gastric residual was 15.9 ± 6.2 % (SEM), and the percentage in colon was 49.6 ± 7.8 %; in 11/12 participants, liquid had entered colon within 2h. Average CAP arrival time in colon was 5.16 ± 0.46h (mode 6 h). After LF, mannitol was extensively absorbed in the first 8h; lactulose absorption was low thoughout the 24h. After the LF, the LMR (geometric mean, 95% CI/hour) in NIH Public Access Author ManuscriptNeurogastroenterol Motil. Author manuscript; available in PMC 2011 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the 0-2h urine was 0.08 [0.05, 0.11]), which was lower than in 8-24h urine (0.32,[0.16, 0.46]; p<0.05). Urine LMRs at 8-24h were similar after LF or CAP. We concluded that, after LF, sugar excretion in 0-2h urine may reflect both SI and colon permeability. Colonic permeability is reflected by urine sugar excretion between 6 and 24h. CAP delivery reduces mannitol excreted at 0-6h, compared to LF. The 0 to 5 or 6h 2-SE urine likely reflects both SI and colon permeability; the higher LMR in the 8-24h urine relative to 0-2h urine should be interpreted with caution and does not mean that colon is more permeable than SI. Keywordsbarrier; irritable bowel; inflammation; LMR Differential absorption and excretion of molecular probes provide evidence of altered permeability of the intestine in gastrointestinal diseases including celiac disease, Crohn's disease and irritable bowel syndrome (IBS). Greater paracellular permeability could facilitate passage of luminal antigens, leading to local mucosal immune responses and resulting in inflammation (1) or stimulation of bowel dysfunction or visceral pain.Some highly sensitive methods for measuring intestinal permeability are too invasive to be used routinely. Ussing chamber techniques, requiring multiple intestinal mucosal biopsies at different levels of the gut, are too invasive to be used in large scale research on humans or for clinical diagnosis (2). Measurements using a single molecule (such as 51 Cr EDTA) are potentially affected by interindividual differences not related to permeability (e.g. transit or urinary excretion). Thus, human intestinal permeability has been measured by urinary excretion of two probes of different sizes but similar transit and uptake processes, and calculating the excretion ratio of a monosaccharide and a disaccharide such as mannitol and lactulose respectively (3). The amounts of lactulose and mannitol in the normal diet are negligible to trace. Other molecules are used, including sucralose. This is an artificial sweetener, ...

Background Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhea and irritable bowel syndrome with diarrhea (IBS-D). Serum 7α-hydroxy-4-cholesten-3-one (7αHCO, or 7αC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the 75SeHCAT retention test. Aim To develop a serum 7αC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn’s disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Methods Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn’s disease, and 20 with distal ileal resection for Crohn’s disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. Results The HPLC-MS/MS assay showed good linearity in concentration range 0–200 ng/mL, sensitivity (lowest limit of detection 0.04 ng/mL), and high analytical recovery (average 99%, range 93–107%). The 5th to 95th percentile for 111 normal healthy controls was 6–60.7 ng/mL. There were significant overall group differences (ANOVA on ranks p<0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (ANOVA p=0.043) with higher mean values in IBS-D relative to controls (rank sum test, p=0.027). Conclusions We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7αC4 values, and identified increased 7αC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a noninvasive test for BAM in IBS.

The overall prevalence of CD increased between 1988 and 2012 and is significantly more common in whites. In addition, a higher proportion of individuals maintaining a gluten-free diet in the absence of a diagnosis of CD are blacks.

Structured Summary Background Olmesartan-associated enteropathy (OAE) is characterized by diarrhea, nausea, vomiting, abdominal pain, weight loss, and severe sprue-like enteropathy, all of which is resolved after olmesartan medoxomil discontinuation. Aim To determine the mechanistic similarities with celiac sprue. Methods Duodenal biopsies were extracted from OAE patients before (n=11) or after (n=17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were 7 “on/off” paired samples. Formalin fixed biopsies were stained for CD8, CD4, FoxP3, IL-15R, and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL-15, IL-15R, and ZO-1. Results In the “on olmesartan medoxomil” duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in olmesartan medoxomil-treated Caco-2 cells. Conclusions OAE shares many features with celiac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effect of gluten upon the epithelium of celiac patients.