Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients.

BACKGROUND: Increased intestinal permeability was described in several intestinal auto-immune conditions. There are very few and contradictory reports about type I diabetes mellitus, an auto-immune condition sometimes associated with celiac disease. AIMS: To investigate intestinal permeability in type I diabetes mellitus patients with no concomitant celiac disease, with a comparison to ultra-structural aspects of duodenal mucosa. PATIENTS: 46 insulin dependent diabetes mellitus, non-celiac, patients (18 females and 28 males, mean age 15.8 +/- 5.3 [S.D.] years) were enrolled. The mean duration of the disease was 5.7 years. METHODS: The morphological aspect of the small bowel mucosa, at standard light microscopy and electron transmission microscopy, along with intestinal permeability (by lactulose/mannitol test) were studied. Lactulose and mannitol urinary excretion were determined by means of high performance anion exchange chromatography-pulsed amperometric detection. RESULTS: The lactulose/mannitol ratio was 0.038 [0.005-0.176] (median and range) in 46 patients compared to 0.014 [0.004-0.027] in 23 controls: insulin dependent diabetes mellitus group values being significantly higher than those of the controls (P < 0.0001, Mann-Whitney test). Eight insulin dependent diabetes mellitus patients underwent endoscopy and biopsies were analysed by means of light microscopy and transmission electron microscopy. At the light microscopy level, none of the biopsy samples showed any sign of atrophy nor inflammation, whereas transmission electron microscopy analysis showed remarkable ultra-structural changes in six out of the eight patients. Four parameters were evaluated: height and thickness of microvilli, space between microvilli and thickness of tight junctions. CONCLUSIONS: This alteration of intestinal barrier function in non-celiac type I diabetes mellitus, frequently associated with mucosal ultra-structural alterations, could suggest that a loss of intestinal barrier function can be a pathogenetic factor in a subset of insulin dependent diabetes mellitus patients.

Intestinal permeability is decreased 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 age-matched 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.

Intestinal permeability assessment before and after ileal pouch-anal anastomosis.

AIM: Intestinal permeability is considered an index of anatomic and functional integrity of the small intestine mucosa. Altered intestinal permeability has been suggested to be a possible cause of pouchitis. Aim of this paper was to assess variations in intestinal permeability during the first year of a pouch reconstruction. METHODS: Intestinal permeability (IP) was investigated in 8 ulcerative colitis patients before and after total proctocolectomy, with ileal pouch-anal anastomosis (IPAA), by means of the cellobiose/mannitol test. To each patient a basal test (before surgery) and 3 more tests during a 1 year follow-up were administered. RESULTS: Individual data were altered despite clinical findings in 9 of 30 IP measured values. An overall pattern of unaffected permeability was however shown and none of our patients, during the first year follow-up, has developed pouchitis. CONCLUSIONS: Six of the 8 investigated patients presented at least 1 altered IP value. A longer follow-up aimed to further investigate patients beyond the first year after IPAA confection as to the occurrence of pouchitis and its possible correlation with a previous permeability alteration of the pouch mucosa is in progress.

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.

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 Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's 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%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's 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 Crohn's 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 Crohn's disease and their relatives.

Altered intestinal permeability to mannitol in diabetes mellitus type I.

BACKGROUND: Intestinal permeability has seldom been investigated in diabetes mellitus, even though patients frequently report gastrointestinal symptoms, and it has recently been shown that the prevalence of celiac disease associated with diabetes mellitus is higher than expected. METHODS: Intestinal permeability to cellobiose and mannitol was investigated in 31 patients affected by type I uncomplicated diabetes mellitus. Values were compared with those obtained in 32 normal subjects. RESULTS: The percentage of mannitol recovery was far higher than normal in two thirds of the investigated patients and correlated with the length of disease, even though the probes' ratio (cellobiose/mannitol) was in the normal range. CONCLUSIONS: A not previously reported increase of intestinal permeability to mannitol, clear-cut and not associated with that of the larger probe, is found in type I uncomplicated diabetes mellitus. These results may describe a primary feature of type I diabetes mellitus and the initial steps of evolution to celiac disease.

Intestinal permeability and diabetes mellitus type 2.

BACKGROUND: Intestinal permeability can be investigated by means of molecular probes which are able to cross the intestinal wall through tight junctions of villi (smaller probes) and/or of crypts (larger probes). Intestinal permeability is altered in the majority of uncomplicated diabetes mellitus type 1 patients, due to the augmented absorption of the smaller probe. The aim of this work was to investigate if any similar alteration of intestinal permeability is present in diabetes mellitus type 2. METHODS: Intestinal permeability was studied by means of the Cellobiose/Mannitol test (CE/MA). The first and larger probe (Cellobiose) crosses tight junctions of crypts, the smaller (Mannitol) crosses those of villi. The CE/MA test was administered to 18 patients affected by diabetes mellitus type 2, with length of disease = 4.5+/-1.9 years (mean+/-SD) with no relevant intestinal pathologies. Results obtained in these 18 patients were compared with those of 25 healthy volunteers. RESULTS: Intestinal permeability to the CE/MA test was normal in all patients. All the investigated permeability parameters (%CE, %MA, CE/MA) overlapped, as a mean, with those of control subjects and were not statistically different. CONCLUSIONS: The present data confirm that diabetes mellitus type 2 has not pathophysiological components at intestinal level. This is different from what was demonstrated in diabetes mellitus type 1, the last being very well known to be associated with autoimmune diseases and celiac disease.

Assessment of small intestinal damage in patients treated with pelvic radiotherapy.

Pelvic radiotherapy almost always induces intestinal symptoms. We investigated the radiation-induced damage to the small intestinal mucosa and evaluated its relationship with symptoms, using cellobiose/mannitol permeability test (CE/MA) and plasma postheparin diamine oxidase test (PHD) in 20 patients treated with pelvic radiotherapy. The symptoms developed during radiotherapy were noted. Intestinal permeability significantly (p=0.013) increased from 0.021 +/- 0.026 to 0.047 +/- 0.055 (mean +/- SD) after 15 days of radiotherapy, while it returned to normal values (0.010 0.015) at the end of radiotherapy. PHD values did not change. All patients developed intestinal symptoms. These findings indicate that pelvic radiotherapy induces an early small bowel mucosa damage followed by mucosal adaptation. Acute intestinal symptoms during pelvic radiotherapy may not depend only on small intestinal mucosal damage.