No abstract

Seventeen paediatric patients with immunodeficiency syndromes (10 with selective IgA deficiency, four with panhypogammaglobulinaemia, and three with selective T cell deficiency) were investigated for bacterial overgrowth of the small intestine and gut permeability to macromolecules. Five of 12 patients showed viable bacterial counts of more than 2 x 105/ml in jejunal fluid. Bacterial overgrowth was also confirmed indirectly by breath hydrogen determination, which was higher than 10 ppm in four of the five patients with positive jejunal culture. Gut permeability to lactulose and L-rhamnose was abnormal in 16 of the 17 immunodeficient patients, who also had higher mean urinary excretion ratios than control subjects -mean (SD) values were 0216 (0.160) and 0-029 (0.002), respectively. These studies indicate that bacterial overgrowth of the small intestine is a common feature in immunodeficient patients, regardless of the immunological abnormality. Moreover, these patients have an increased gut permeability to macromolecules.

To define the action of deconjugated bile acids on the small intestinal permeability in an in vitro system, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a dose-related manner the transepithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.

The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12-3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose:L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten chalienges may be an added contribution to the accuracy of the diagnosis in childhood.

The antirejection drug tacrolimus (FK506) has been reported to impair intestinal permeability in an early stage after orthotopic liver transplantation (OLT), and cyclosporine (CsA) has shown a similar effect in animals. We studied the chronic effect of FK506 and CsA on gastroduodenal and intestinal permeability and on blood endotoxin levels in patients 2 to 3 years after OLT. Thirty-two OLT patients (22 men and 10 women; mean age, 44.8 ؎ 7.1) who had received CsA (n ‫؍‬ 19) or FK506 (n ‫؍‬ 13) and 10 healthy volunteers (6 male and 4 female, mean age 41.7 ؎ 5.4) were assessed for gastroduodenal permeability by recovery in urine of sucrose after oral administration and for intestinal permeability by recovery in urine after oral loads of rhamnose and lactulose, which evaluate the intracellular and paracellular routes, respectively. In all subjects, plasma levels of endotoxins also were assessed. Gastroduodenal permeability was similar in patients and controls (0.03 ؎ 0.003 versus 0.04 ؎ 0.01%, P ‫؍‬ NS). In regard to intestinal permeability, passage through the intracellular route was significantly reduced in OLT patients compared with controls (1.13 ؎ 0.06 versus 2.74 ؎ 0.17%, P < .01), but paracellular permeability was unchanged (0.14 ؎ 0.007 versus 0.13 ؎ 0.01%, P ‫؍‬ NS). Serum endotoxin levels were similar in all subjects. We conclude that chronic administration of FK506 or CsA induces a clinically irrelevant, selective dysfunction of monosaccharide absorption, but does not affect gastroduodenal or intestinal permeability. (Liver Transpl 2003;9:484-488.) D uring the last decade, an increasing number of subjects underwent orthotopic liver transplantation (OLT). 1 In Europe, the average survival rate 1 year after OLT currently is over 80%, and morbidity and mortality rates after transplantation are receiving increasing attention. 1 Infections, neoplasms and autoimmune disease, and a higher risk of hypertension and lipid abnormalities usually are observed after OLT, and all can negatively affect the outcome of the transplant. 2,3 Most of the metabolic alterations observed after OLT likely are associated with the use of immunosuppressive drugs, and various side effects have been reported during chronic therapy with cyclosporine (CsA) and tacrolimus (FK506). 4,5 During immunosuppressive and cytotoxic therapy, the intestinal epithelium can lose its barrier function. 6,7 This function can be evaluated in vivo by tests based on permeability of small intestine to sugar probes such as lactulose (Lacl) and rhamnose (L-Rh), administered orally and recovered in urine. 8 The ratio between urinary Lacl and L-Rh has been used to evaluate altered intestinal permeability in conditions such as immunodepression, 9,10 viral gastroenteritis, 11,12 coeliac disease, 13 and Crohn's disease. 14 In these conditions, the increased permeation of macromolecules through the intestinal wall takes place generally through the paracellular pathway and may be associated with high levels of plasmatic endotoxins. 15,16 FK506 has been reported to i...