M. Secondulfo

Intestinal permeability in Crohn's disease patients and their first degree relatives.

BACKGROUND Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohns disease. AIM Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohns disease. SUBJECTS 16 Crohns disease patients and 26 of their cohabiting first degree relatives were studied. METHODS To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohns disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohns disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohns disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohns disease and their relatives.

Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer.

5-Fluorouracil (5-FU), in association with leucovorin (LV), is the most used chemotherapy agent in the treatment of colorectal cancer. Response rate, as well as side-effect incidence, increases with the dose intensity of regimens that are used. The most common dose-limiting toxicity for 5-FU/LV modulation is diarrhea. To assess the modification of small intestinal function, we investigated the changes in intestinal permeability (IP) and intestinal absorption (IA) in 41 chemo-naive patients (21 men and 22 women; mean age, 61 ± 9 years) with advanced colorectal cancer after treatment with the association of folinic acid and 5-FU. After chemotherapy administration, we found a marked increase in IP and a reduction in IA, measured as cellobiose–mannitol (CE–MA) ratio (p < 0.0001) and D-xylose absorption (p = 0.0001), respectively. Patients who experienced diarrhea have an increase in CE–MA ratio and a reduction in D-xylose absorption values, both statistically significant. Cellobiose–mannitol ratio and D-xylose absorption tests can be used for the assessment of toxic effect of 5-FU on mature intestinal epithelium and also for evaluating the role of cytoprotective agents.

Cellobiose and lactulose coupled with mannitol and determined using ion-exchange chromatography with pulsed amperometric detection, are reliable probes for investigation of intestinal permeability

Lactulose/mannitol and cellobiose/mannitol tests are currently used in the investigation of intestinal permeability (IP) in many gastrointestinal diseases. The aim of this study was to produce a good technique for the determination and comparison of the above-mentioned sugar probes to overcome the problem caused by the presence of significant glycosuria in patients affected by particular metabolic disorders such as diabetes mellitus. Tests were performed in 25 healthy volunteers, using either cellobiose (Ce) (5 g) and mannitol (Ma) (2 g), or lactulose (La) (5 g) and mannitol (2 g), given as oral isosmolar loads. Sugars were recovered in urine collected for 5 h. Analysis was carried out by using anion-exchange chromatography (AEC) with pulsed amperometric detection (PAD). Baseline separation of the above carbohydrates was achieved within 13 min by using a Carbopac PA-100 column and linear gradient elution. Carbohydrate quantification was performed by an internal standard method. The calibration curve for each sugar is linear to 40 mM. The limit of sugar detection is 0.01 mM. Recovery of sugar probes is between 98.2 and 100%. The %La, %Ce, %Ma in urine were evaluated and their ratios (Ce/Ma and La/Ma) were calculated. No significant difference in IP parameters were shown (La/Ma to Ce/Ma 0.018+/-0.014 vs. 0.012+/-0.007; the attendant probability of the null hypothesis being P=0.0714). Ce/Ma and/or La/Ma tests result similarly reliable in the clinical investigation of IP and the described new method is also helpful in urine even with high glucose concentration, without any interference.

Assessment of intestinal permeability and orocecal transit time in patients with systemic sclerosis: analysis of relationships with epidemiologic and clinical parameters

ObjectiveThe aim of this study was to assess intestinal permeability (IP) in patients with systemic sclerosis (SSc) and to relate the results with general disease activity and gastrointestinal involvement.MethodsTwenty-eight females and four males were studied. Patients with severe gastrointestinal involvement were excluded. Thirty-three healthy volunteers served as controls. Intestinal permeability was assessed by means of the orally administered cellobiose/mannitol sugar (Ce/Ma) test. Intestinal transit time (ITT) was investigated with the H2-lactulose breath test.ResultsThe mean value of IP in 32 SSc patients was significantly higher than in 33 controls (P<0.05), although it fell within the normal range. Eleven patients showed abnormally high individual IP values (>0.028) that significantly correlated to disease duration (r=0.73). Altered IP was associated with the higher but not statistically relevant presence of anti-Scl70 antibodies (9/11) and to more severe gastrointestinal involvement. More than half of the SSc patients showed slower orocecal transit times on the H2 breath test. In particular, delayed ITT was observed in 60% of patients with increased IP and in all patients with moderate gastrointestinal involvement according to the scleroderma severity scale.ConclusionIntestinal permeability was altered in 11/32 SSc patients. Correlations between increased IP and duration of disease and degree of gastgrointestinal involvement appear to support the hypothesis of secondary involvement of the intestinal barrier, and the presence of anti-Scl70 antibodies in 82% of the patients with higher IP clearly reinforces the hypothesis of an altered immune response in these subjects.

Intestinal permeability is deveeased in anorexia nervosa

Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free agematched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa. Molecular Psychiatry (2004) 9, 76‐80. doi:10.1038/sj.mp.4001374