Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15 percent) and healthy controls (0.42 vs 0.07 percent). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07 percent). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21 percent) and these values were significantly higher than in celiac disease patients (10.9 percent). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil.

To examine the association of intestinal barrier function with vitamin A deficiency and whether supplementation of micronutrients improves intestinal function and/or linear growth, height-for-age z-score (HAZ), concentrations of serum retinol and zinc, and intestinal permeability were determined in a cross-sectional sample of 75 children in northeastern Brazil. Effects of vitamin A and supplementation of zinc on intestinal permeability and growth were also determined comparing results before and after treatment in 20 children and age-matched controls. Lactulose:mannitol (L/M) permeability ratios inversely correlated with serum retinol concentrations (r = -0.55, p < 0.0005). Increased L/M permeability ratios with reduced concentrations of serum retinol were predominantly attributable to lower absorption of mannitol (r = 0.28, p = 0.02). L/M permeability ratios (p = 0.001) and HAZ scores (p = 0.007) improved with supplementation. It is concluded that impaired intestinal barrier function and linear growth shortfalls improve following supplementation of vitamin A and zinc in this setting.

Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases

The excretion ratio of lactulose/mannitol in urine has been used to assess the extension of malabsorption and impairment of intestinal permeability. The recovery of lactulose and mannitol in urine was employed to evaluate intestinal permeability in children with and without diarrhea. Lactulose and mannitol probes were measured using high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD). Two groups of solutions containing 60 µM sugars were prepared. Group I consisted of glucosamine, mannitol, melibiose and lactulose, and group II of inositol, sorbitol, glucose and lactose. In the study of intra-experiment variation, a sample of 50 µl from each group was submitted to 4 successive determinations. The recovered amounts and retention times of each sugar showed a variation <2 and 1 per cent, respectively. The estimated recovery was >97 per cent. In the study of inter-experiment variation, we prepared 4 independent samples from groups I and II at the following concentrations: 1.0, 0.3, 0.1, 0.03 and 0.01 mM. The amounts of the sugars recovered varied by <10 per cent, whereas the retention times showed an average variation <1 per cent. The linear correlation coefficients were >99 per cent. Retention (k'), selectivity (a) and efficiency (N) were used to assess the chromatographic conditions. All three parameters were in the normal range. Children with diarrhea presented a greater lactulose/mannitol ratio compared to children without diarrhea.

Permeabilidad intestinal en alcohólicos sin daño hepático / Intestinal permeability in alcoholics without hepatic damage

Methods: Thirty seven male subjects were studied, 18 controls and 19 alcoholic: All subjects underwent an anthropometric assessment and dietary history. Lactulose/mannitol test was performed during the third day of abstinence in alcoholics. After an 8 hour overnight fast, subjects drank 200 ml of a solution containing 56 g lactulose and 5 g mannitol. Subsequently, urine was collected during the following 5 hours, where both sugars were measured by gas chromatography. Results: Median values of lactulose/mannitol ratio were similar in alcoholics and controls (0.011, range 0.005-0.071 vs 0.014, range 0.005-0.027 respectively). However, absolute urinary excretion of both lactulose and mannitol was lower in alcholics. There was no relationship betwwen nutritional status and urinary excretion of lactulose, mannitol or lactulose/mannitol ratio. Conslusion: In this alcoholic patients, no changes were observed in intestinal permability