The effect of an acute aspirin challenge on intestinal permeability in healthy adults with and without prophylactic probiotic consumption: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: Healthy individuals may experience increases in intestinal permeability after chronic or acute use of non-steroidal anti-inflammatory drugs, which may be attenuated by probiotics. This study investigates the effects of an acute aspirin challenge on gastroduodenal barrier function with or without prophylactic probiotic consumption. METHODS: Twenty-nine generally healthy participants (26 ± 6 years) completed a 14-week randomized, double-blind, crossover trial. A probiotic containing 2 Lactobacilli strains or placebo was administered for 3 weeks, with a 4-week washout period between crossover phases. Daily and weekly questionnaires assessing gastrointestinal function were completed for 2 weeks before until 2 weeks after each intervention to assess gastrointestinal function. Gastroduodenal permeability was assessed by urinary excretion of orally administered sucrose after 1, 2, and 3 weeks of each intervention with a 1950 mg-aspirin challenge after 2 weeks of supplementation. Stool samples were collected weekly during supplementation for detection of species of interest. RESULTS: Gastroduodenal permeability increased with aspirin challenge (Week 1: 3.4 ± 0.6 µmol vs Week 2: 9.9 ± 1.0 µmol urinary sucrose; p < 0.05). There were no differences in the change in permeability after the aspirin challenge or gastrointestinal function between interventions. CONCLUSION: The acute aspirin challenge significantly increased intestinal permeability similarly in both groups, and prophylactic probiotic consumption was unable to prevent the loss in this particular model.

Sucrose-Powered Liposome Nanosensors for Urinary Glucometer-Based Monitoring of Cancer.

Timely detection of early-stage cancer holds immense potential in enhancing prognostic outcomes. There is an increasing desire for versatile tools to enable simple, sensitive, and cost-effective cancer detection. By exploiting the extraintestinal metabolic inertness and efficiency renal clearance of sucrose, we designed a liposome nanosensor using sucrose as a messenger to convert tumor-specific esterase activity into glucose meter readout, enabling economical and sensitive urinalysis for cancer detection in point-of-care testing (POCT). Our results demonstrate that the nanosensors exhibited significant signal differences between tumor-bearing and healthy mice in both orthotopic and metastatic tumor models. Additionally, efficient elimination of the nanosensors through the hepatobiliary pathway was observed with no significant toxicity. Such a non-invasive diagnostic modality significantly assists in personalized pharmacological treatment and follow-up efficacy assessment. We envision that this modular liposome nanosensor platform might be applied for economically detecting diverse diseases via a simple urinary test.

Intestinal barrier function in morbid obesity: results of a prospective study on the effect of sleeve gastrectomy.

BACKGROUND: Obesity has been associated with impaired intestinal barrier function. It is not known whether bariatric surgery leads to changes in intestinal barrier function. We hypothesized that obesity is associated with disturbances in gastrointestinal barrier function, and that after bariatric surgery barrier function will improve. METHODS: Prospective single center study in which we assessed segmental gut permeability by urinary recovery of a multisugar drink in 27 morbidly obese (BMI 43.3 ± 1.1 kg/m2) and 27 age and gender matched lean subjects (BMI 22.9 ± 0.43 kg/m2). Fecal calprotectin, SCFAs, plasma cytokines, and hsCRP were assessed as inflammatory and metabolic markers. Comparisons: (a) morbidly obese subjects vs. controls and (b) 2 and 6 months postsleeve vs. presleeve gastrectomy (n = 14). In another group of 10 morbidly obese and 11 matched lean subjects colonic and ileal biopsies were obtained in order to measure gene transcription of tight junction proteins. RESULTS: Gastroduodenal permeability (urinary sucrose recovery) was significantly increased in obese vs. lean controls (p < 0.05). Small intestinal and colonic permeability (urinary recovery of lactulose/L-rhamnose and sucralose/erythritol, respectively) in obese subjects were not significantly different from controls. Morbidly obese subjects had a proinflammatory systemic and intestinal profile compared with lean subjects. After sleeve gastrectomy BMI decreased significantly (p < 0.001). Postsleeve gastroduodenal permeability normalized to values that do not differ from lean controls. CONCLUSIONS: Gastroduodenal permeability, but not small intestinal or colonic permeability, is significantly increased in morbidly obese patients. After sleeve gastrectomy, gastroduodenal permeability normalized to values in the range of lean controls. Thus, the proximal gastrointestinal barrier is compromised in morbid obesity and is associated with a proinflammatory intestinal and systemic profile.

Urinary sucrose and fructose to validate self-reported sugar intake in children and adolescents: results from the I.Family study.

PURPOSE: Excessive consumption of free sugar increases the risk for non-communicable diseases where a proper assessment of this intake is necessary to correctly estimate its association with certain diseases. Urinary sugars have been suggested as objective biomarkers for total and free sugar intake in adults but less is known about this marker in children and adolescents. Therefore, the aim of this exploratory study is to evaluate the relative validity of self-reported intake using urinary sugars in children and adolescents. METHODS: The study was conducted in a convenience subsample of 228 participants aged 5-18 years of the I.Family study that investigates the determinants of food choices, lifestyle and health in European families. Total, free and intrinsic sugar intake (g/day) and sugar density (g/1000 kcal) were assessed using 24-h dietary recalls (24HDRs). Urinary sucrose (USUC) and urinary fructose (UFRU) were measured in morning urine samples and corrected for creatinine excretion (USUC/Cr, UFRU/Cr). Correlation coefficients, the method of triads and linear regression models were used to investigate the relationship between intake of different types of sugar and urinary sugars. RESULTS: The correlation between usual sugar density calculated from multiple 24HDRs and the sum of USUC/Cr and UFRU/Cr (USUC/Cr + UFRU/Cr) was 0.38 (p < 0.001). The method of triads revealed validity coefficients for the 24HDR from 0.64 to 0.87. Linear regression models showed statistically significant positive associations between USUC/Cr + UFRU/Cr and the intake of total and free sugar. CONCLUSIONS: These findings support the relative validity of total and free sugar intake assessed by self-reported 24HDRs in children and adolescents.

Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study.

BACKGROUND: Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(-)] increased s-IP according to normal or altered La/Ma ratio. METHODS: The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann-Whitney or the Kruskal-Wallis with Dunn's post-test was used to assess differences among the groups. RESULTS: As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(-) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(-) ones. CONCLUSIONS: The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population. TRIAL REGISTRATION: NCT01574209 . Registered March 2012. First recruitment started in April 2012.

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat.

The aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40-day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener.

High-Throughput Metabolomics for Discovering Potential Metabolite Biomarkers and Metabolic Mechanism from the APPswe/PS1dE9 Transgenic Model of Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disorder, is the major form of dementia. As AD is an irreversible disease, it is necessary to focus on earlier intervention. However, the potential biomarkers of preclinical AD are still not clear. In this study, urinary metabolomics based on ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was performed for delineating the metabolic changes and potential early biomarkers in APPswe/PS1dE9 (APP/PS1) transgenic mice. A total of 24 differentially regulated metabolites were identified when comparing transgenic mice to wild-type mice using multivariate statistical analysis. Among them, 10 metabolites were significantly upregulated and 14 metabolites were downregulated. On the basis of these potential biomarkers, metabolic pathway analysis found that pentose and glucuronate interconversions, glyoxylate and dicarboxylate metabolism, starch and sucrose metabolism, the citrate cycle, tryptophan metabolism, and arginine and proline metabolism were disturbed in APP/PS1 mice. Our study revealed that levels of endogenous metabolites in the urine of APP/PS1 mice changed prior to the emergence of learning and cognitive impairment, which may be associated with abnormal nitric oxide production pathways and metabolic disorders of monoaminergic neurotransmitters. In conclusion, this study showed that metabolomics provides an early indicator of disease occurrence for AD.

Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012.

Methadone plays an increasing role in drug-related deaths in Hamburg. To find out whether intravenous application of methadone plays a relevant role in methadone-related deaths, body fluids of all methadone-positive cases (n=130) and three buprenorphine-positive cases where a urine sample was available (n=58+3) were investigated for disaccharides (sucrose and lactose as markers for intravenous methadone abuse). Sixty-four percent of the urine samples of the methadone cases showed positive results for disaccharides (22 times sucrose alone, range 2 to >1,000 mg/L; 6 times lactose and sucrose; and 9 times lactose alone, range 22 to 382 mg/L). The three buprenorphine cases showed positive results for lactose in urine. In blood, it was not possible to detect any disaccharides. Of the 116 fatal methadone intoxications, 49 % were under opiate maintenance treatment (OMT) at the point of death (A-OMT), 30 % were never in OMT (N-OMT) and 21 % were formerly in an OMT, but not at the point of death (F-OMT). Of the deceased in the OMT group, 12 % (n=7) died within the first 2 weeks of treatment, six of them within the first week. Overall, intravenous abuse of methadone plays a relevant role in methadone-related fatal cases of substituted patients and of drug consumers not in therapy. Thus, it is necessary that therapists keep to the statutory regulations and give take-home doses only after at least 6 months of successful therapy and when there is no suspicion of intravenous abuse.

Influence of urine volume on the assessment of intestinal permeability in affected children by multiple sugar probes.

BACKGROUND: In this study we have looked at the reliability of a multi-sugar test in a pediatric patient population and its accuracy at small urine volumes to evaluate intestinal permeability. METHODS: Out of 117 subjects enrolled, 31 were healthy and 86 were sick. A solution containing lactulose, rhamnose, sucrose, and sucralose was administered to subjects who were on fasting; the urine excreted during 5 h was collected and measured. Samples were analyzed by gas chromatography-tandem mass spectrometry and results were expressed as percentage of sugar recoveries and lactulose/rhamnose (L/R) ratio. RESULTS: The analyses showed a clear effect of low urinary volumes (≤240 mL) particularly affecting rhamnose excretion in healthy subjects and sucrose and sucralose recovery in diseased children. Despite the low rhamnose recovery, as lactulose is not similarly affected, the diagnostic reliability of L/R ratio is well preserved at low diuresis conditions. However, this ratio can be useful to discriminate acute conditions vs. clinical remissions only at high urine volumes. Data also suggest potential diagnostic applicability of sucrose and sucralose in children at high urine volumes. CONCLUSIONS: In conclusion, the multi-sugar test has a good predictivity in pediatric subjects but results must be carefully interpreted in the face of reduced diuresis.

Relative validity of habitual sugar and low/no-calorie sweetener consumption assessed by food frequency questionnaire, multiple 24-h dietary recalls and urinary biomarkers: an observational study within the SWEET project.

BACKGROUND: Studies investigating associations between sweeteners and health yield inconsistent results, possibly due to subjective self-report dietary assessment methods. OBJECTIVES: We compared the performance of a food frequency questionnaire (FFQ), multiple 24-h dietary recalls (24hRs), and urinary biomarkers to estimate intake of sugars and low/no-calorie sweeteners (LNCSs). METHODS: Participants (n = 848, age 54 ± 12 y) from a 2-y observational study completed 1 semiquantitative FFQ and ≥ 3 nonconsecutive 24hRs. Both methods assessed intake of sugars (mono- and disaccharides, sucrose, fructose, free and added sugars) and sweetened foods and beverages (sugary foods, fruit juice, and sugar or LNCS-containing beverages [sugar-sweetened beverages and low/no-calorie sweetened beverages (LNCSBs)]); 24hRs also included LNCS-containing foods and tabletop sweeteners (low/no-calorie sweetened foods [LNCSFs]). Urinary excretion of sugars (fructose+sucrose) and LNCSs (acesulfame K+sucralose+steviol glucuronide+cyclamate+saccharin) were simultaneously assessed using ultrapressure liquid chromatography coupled to tandem mass spectrometry in 288 participants with 3 annual 24-h urine samples. Methods were compared using, amongst others, validity coefficients (correlations corrected for measurement error). RESULTS: Median (interquartile range) FFQ intakes ranged from 0 (0-7) g/d for LNCSBs to 94 (73-117) g/d for mono- and disaccharides. LNCSB use was reported by 32% of participants. Median LNCSB+LNCSF intake using 24hRs was 1 (0-50) g/d and reported by 58%. Total sugar excretions were detected in 100% of samples [56 (37-85) mg/d] and LNCSs in 99% of urine samples [3 (1-10) mg/d]. Comparing FFQ against 24hRs showed VCs ranging from 0.38 (fruit juice) to 0.74 (LNCSB). VCs for comparing FFQ with urinary excretions were 0.25 to 0.29 for sugars and 0.39 for LNCSBs; for 24hR they amounted to 0.31-0.38 for sugars, 0.37 for LNCSBs, and 0.45 for LNCSFs. CONCLUSIONS: The validity of the FFQ against 24hRs for the assessment of sugars and LNCSBs ranged from moderate to good. Comparing self-reports and urine excretions showed moderate agreement but highlighted an important underestimation of LNCS exposure using self-reports.

Simultaneous determination of lactulose, sucrose, sucralose, and mannitol using high-performance liquid chromatography-refractive index to estimate intestinal permeability in patients with active ulcerative colitis.

OBJECTIVES: The intestinal permeability (IP) of sugars and their derivatives has been widely used to assess mucosal damage in gastrointestinal diseases. Ulcerative colitis (UC) is a recurring and relapsing disease that causes inflammation of the gut. IP of sugars can be evaluated and correlated with the flare of UC. MATERIALS AND METHODS: A prospective study was conducted on 91 patients with active UC at the tertiary care center in North India. Mayo grading system assessed disease activity, and IP was assessed by measuring sucrose, lactulose, mannitol, and sucralose in urine samples from UC patients. A high-performance liquid chromatography (HPLC) method to detect all of these sugars simultaneously using a refractive index detector was developed and further validated in patients with UC. RESULTS: The analytical recovery rate of the tested sugars ranged from 95% to 146% in the urine matrix. The limit of detection and limit of quantification were 78.838 mg/L and 262.79 mg/L for sucrose, 84.994 mg/L and 283.31 mg/L for lactulose, 74.789 mg/L and 249.30 mg/L for mannitol, and 50.908 mg/L and 169.69 mg/L for sucralose. CONCLUSION: The standardized HPLC method is sensitive and suitable for the simultaneous detection and determination of different sugar moieties in the urine sample. Patients with UC can be evaluated indirectly for the flare by estimating the recovery rate of sugars through gut permeability. The procedure is noninvasive and thus improves the quality of life of chronically ill patients.

The effect of probiotics on gastric mucosal permeability in humans administered with aspirin.

OBJECTIVE: To examine whether a probiotic strain, Lactobacillus gasseri OLL2716 (LG21), can protect the gastric mucosal integrity from aspirin using urinary sucrose excretion (USE) test. MATERIALS AND METHODS: In the study using high-dose aspirin, the USE tests were carried out in 29 volunteers before and after LG21 treatment for 4 weeks. In the study using patients undergoing low-dose aspirin therapy, USE tests were performed in 37 subjects who took LG21 for 16 weeks. Stool occult blood was examined by the guaiac method. RESULTS: In the former study, the elevation in the USE value after aspirin loading significantly decreased after LG21 treatment (Median ± SD; 0.244 ± 0.237 vs. 0.208 ± 0.112%, p = 0.018). In the latter study, the USE value significantly decreased in the period with LG21 treatment (p = 0.033), while no significant difference was found in the period without LG21 (p = 0.113). The number of positive occult blood tests decreased during LG21 treatment. CONCLUSIONS: The regular ingestion of LG21 may protect the integrity of the gastric mucosal permeability against aspirin.

Is moderate red wine consumption safe in inactive inflammatory bowel disease?

BACKGROUND: Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. METHODS: To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1-3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. RESULTS: No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). CONCLUSIONS: One week of moderate consumption of red wine in inactive IBD was associated with a significant decrease in stool calprotectin and a significant increase in intestinal permeability. Our data suggests that patients with inactive IBD who drink red wine daily may be at an increased long-term risk for disease relapse.

Investigating the performance of 24-h urinary sucrose and fructose as a biomarker of total sugars intake in US participants - a controlled feeding study.

BACKGROUND: Developing approaches for the objective assessment of sugars intake in population research is crucial for generating reliable disease risk estimates, and evidence-based dietary guidelines. Twenty-four-hour urinary sucrose and fructose (24uSF) was developed as a predictive biomarker of total sugars intake based on 3 UK feeding studies, yet its performance as a biomarker of total sugars among US participants is unknown. OBJECTIVES: To investigate the performance of 24uSF as a biomarker of sugars intake among US participants, and to characterize its use. METHODS: Ninety-eight participants, aged 18-70 y, consumed their usual diet under controlled conditions of a feeding study for 15 d, and collected 8 nonconsecutive 24-h urines measured for sucrose and fructose. RESULTS: A linear mixed model regressing log 24uSF biomarker on log total sugars intake along with other covariates explained 56% of the biomarker variance. Total sugars intake was the strongest predictor in the model (Marginal R2 = 0.52; P <0.0001), followed by sex (P = 0.0002) and log age (P = 0.002). The equation was then inverted to solve for total sugars intake, thus generating a calibrated biomarker equation. Calibration of the biomarker produced mean biomarker-based log total sugars of 4.79 (SD = 0.59), which was similar to the observed log 15-d mean total sugars intake of 4.69 (0.35). The correlation between calibrated biomarker and usual total sugars intake was 0.59 for the calibrated biomarker based on a single biomarker measurement, and 0.76 based on 4 biomarker repeats spaced far apart. CONCLUSIONS: In this controlled feeding study, total sugars intake was the main determinant of 24uSF confirming its utility as a biomarker of total sugars in this population. Next steps will include validation of stability assumptions of the biomarker calibration equation proposed here, which will allow its use as an instrument for dietary validation and measurement error correction in diet-disease association studies.

Assessment of small-intestine permeability in healthy Nigerian children is altered by urinary volume and voiding status.

OBJECTIVE: This study aimed to uncover the effect of voided urinary volume on small intestine permeability ratios in healthy children. METHODS: We assessed small intestine permeability in 155 apparently healthy children, aged 3-5 years old, without any visible symptoms of disease, in a rural, malaria-endemic setting in Nigeria, using a multi-sugar test solution, comprising lactulose, sucrose, mannitol, and rhamnose. Children were categorized into low urinary volume (LV) and high urinary volume (HV), based on the volume of urine voided per kg body weight per hour. LV children voided less than 25th percentile of the total population, while HV children voided greater than 75th percentile of the total population. Urinary volume excreted over a 90-minute period after administration of the test solution was measured, and differences in sugar ratios were compared between children with high (HV) and low urinary volumes (LV), as well as between children who voided (VC) or who were not able to void (NVC) before administration of the test solution. RESULTS: Urinary mannitol and rhamnose recovery were 44% (p = 0.002) and 77% (p<0.001) higher in HV children compared to LV children respectively, while urinary lactulose recovery was 34% lower (p = 0.071). There was no difference in urinary sucrose recovery between groups (p = 0.74). Lactulose-mannitol ratio, lactulose-rhamnose ratio and sucrose-rhamnose ratio were all significantly higher in children in the LV group compared to children in the HV group (p<0.001). In a multiple regression analysis, urinary volume and voiding status combined, explained 13%, 23% and 7% of the variation observed in lactulose-mannitol, lactulose-rhamnose and sucrose-rhamnose ratios, respectively. CONCLUSION: Sugar permeability ratios vary significantly with total urinary volume in multi-sugar small-intestine permeability tests. Voiding status before sugar administration appears to influence lactulose recovery, lactulose-rhamnose and sucrose-rhamnose ratios independently of total urinary volume. Evidence from this study suggests the need to take urinary volume into account when conducting multi-sugar small-intestine permeability tests.

Effects of timing, sex, and age on site-specific gastrointestinal permeability testing in children and adults.

OBJECTIVES: Measurement of gastrointestinal (GI) permeability is commonly used in research and often used clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and sex on GI permeability testing. We seek to determine the timeframes of sugar excretion and the potential effects of age and sex on urinary recovery of the sugars. SUBJECTS AND METHODS: Healthy adults (n = 17) and children (n = 15) fasted 4 hours after the evening meal and then ingested a solution of sucrose, lactulose, mannitol, and sucralose. Urine was collected at 30, 60, and 90 minutes after ingestion and then each time the subjects voided during the next 24 hours. Each urine void was collected separately. RESULTS: Median age for the adults was 47.5 years (range 21-57 years) and for children 10 years (range 5-17 years). There were no differences between children and adults in mean percent dose of sugar recovered. The time of peak urinary recovery of the sugars was generally similar between children and adults. Sucrose urinary recovery declined with age (P = 0.008; r2 = 0.19) unrelated to sex. Lactulose and sucralose urinary recovery declined with age in females (P = 0.05, r2 = 0.24 and P = 0.011, r2 = 0.41; respectively) but not in males. CONCLUSIONS: Overall, sugar urinary recovery is comparable in children and adults. Specific sugar urinary recovery may change as a function of age and/or sex. These results need to be taken into account when planning and interpreting gastrointestinal permeability studies.

A randomized, double-blind, placebo-controlled trial of rifaximin, a nonabsorbable antibiotic, in the treatment of tropical enteropathy.

OBJECTIVES: Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol (L:M) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity. The etiology of tropical enteropathy is postulated to be intestinal bacterial overgrowth. This study tested the hypothesis that treatment with a nonabsorbable, broad-spectrum antibiotic, rifaximin, reduces the L:M ratio in rural Malawian children, among whom tropical enteropathy is common. METHODS: All children aged 3-5 years from one village were enrolled in a randomized, double-blind, placebo-controlled trial of treatment with rifaximin for 7 days. The L:M ratio was measured before and after treatment, and the change in the L:M ratio was the primary outcome. Secondary outcomes were changes in the urinary sucrose-to-lactulose (SUC:L) and sucralose-to-lactulose (SCL:L) ratios, as well as changes in the fractions of each test sugar recovered in the urine. RESULTS: A total of 144 children participated in this study, of whom 76% had an elevated L:M ratio on enrollment (L:M > or = 0.10). Children who received rifaximin did not show an improvement in their L:M ratio compared with those who received placebo (-0.01+/-0.12 vs. 0.02+/-0.16, respectively, P=0.51, mean+/-s.d.), nor were there significant differences between the two groups in excretion of lactulose, mannitol, sucralose, or sucrose, or in the SUC:L and SCL:L ratios. CONCLUSIONS: Rifaximin had no effect on the tropical enteropathy of 3-5-year-old Malawian children, suggesting that small-bowel bacterial overgrowth is not an important etiological factor in this condition.

Clinical relevance of measuring colonic permeability.

BACKGROUND: Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups. DESIGN: After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG). RESULTS: In controls, sucralose excretion was highly variable (0.67+/-0.92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0.054+/-0.060; 0.323+/-0.253 vs. 0.018+/-0.001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG (r=0.72, and r=0.51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients (P=0.099), sucralose excretion was not related to clinical outcome. CONCLUSIONS: The proposed cut-off for normal sucralose excretion is 2.11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.

Significance of sucrose permeability test in detecting early gastric cancer and changes of permeability after endoscopic mucosal resection.

BACKGROUND/AIMS: To evaluate the diagnostic value of sucrose permeability test (SPT) with special reference to early gastric cancer (EGC), and to assess the changes of urinary sucrose level after treatment of gastric damage: gastric ulcer (GU) or EGC. METHODOLOGY: Ninety subjects were included in this study, that is; 18 patients with GU, 25 EGC, 17 advance gastric cancer (AGC), and 30 healthy volunteers (HV). SPT was conducted before treatment in all the subjects, and in 6 patients each with GU and EGC after treatment- proton pump inhibitor for GU and endoscopic mucosal resection for EGC. Diagnostic values were calculated based on cut-off values estimated from the ROC curves. RESULTS: The mean amount of sucrose excreted into urine in HV, GU, EGC, and AGC was 50.8 +/- 28.0 mg, 225.9 +/- 201.1 mg, 170.2 +/- 86.4 mg, and 426.2 +/- 155.0 mg, respectively, showing significant differences between HV and gastric disease groups (p < 0.01). The sensitivity for detecting GU, EGC, and AGC was 94.4%, 88.0%, and 100%, respectively. Sucrose excretion in GU and EGC was significantly decreased after treatment (262.4 +/- 121.2 to 80.6 +/- 42.1, and 246.0 +/- 136.9 to 139.1 +/- 69.2, p < 0.05 and p < 0.001, respectively). CONCLUSIONS: SPT was considered useful to detect not only GU or AGC but also EGC with a high sensitivity. A significant decrease of sucrose excretion was observed after treatment in EGC.

Colonic permeability is higher in Great Danes compared with smaller breed-dogs.

Fed the same dry diet, large dogs show poorer fecal quality than small ones. A high colonic permeability could explain a low water and electrolyte net balance leading to high fecal water content. This experiment was conducted to evaluate colonic permeability in dogs varying in body size and to determine whether colonic permeability is related to fecal sodium concentration and fecal quality. Four breeds of dogs were used: six Miniature Poodles (MP), six Standard Schnauzers (SS), six Giant Schnauzers (GS) and six Great Danes (GD). Colonic permeability was evaluated using the ratio of urinary lactulose to sucralose (L:S) after oral administration. Fecal sodium concentration was measured by flame photometry. The urinary L:S ratio was significantly lower in GD, indicating a higher colonic permeability, than in the three other breeds (0.35 ± 0.12 for GD and 0.51 ± 0.05 for MP). GD also presented the higher fecal sodium concentrations and the poorest fecal quality. The higher fecal sodium concentration observed in GD could be explained by the higher colonic permeability and both these variables could be important explanations for higher fecal moisture in large dogs.