Intestinal permeability in cystic fibrosis in relation to genotype

The purpose of this study was to investigate whether the increase intestinal permeability (IP) seen in patients with cystic fibrosis (CF) is correlated with the basic defect, as revealed by the patient's genotype, and/or whether the intestinal disturbance reflects secondary abnormalities such as essential fatty acid deficiency.

Nineteen CF patients were compared with nine age- and sex-matched healthy controls. IP was evaluated by studying urinary excretion for 5 hours after a test meal containing lactulose, L-rhamnose and xylose in water. Urine was analyzed for carbohydrates, and blood samples were taken for determination of the fatty acid pattern of serum phospholipids. The CF patients were grouped according to genotype: homozygous for delta F508, heterozygous for alpha F508, or unidentified.

Patients who were homozygous (n = 9) or heterzygous (n = 6) for delta F508 had significantly higher lactulose/L-rhamnose excretion ratios (mean(range) values of 0.08(0.05-0.13) and 0.09(0.03-0.13), respectively) than patients (n = 4) with unidentified genotypes [0.03(0.02-0.05); p = 0.005] or healthy controls [0.02(0.003-0.06); p = 0.002]. CF patients with EFAD (n = 6) did not differ from those with a normal pattern of serum phospholipid fatty acids, the lactulose/L-rhamnose excretion ratio being 0.08(0.02-0.13) and 0.07(0.03-0.12), respectively.

These data show that the IP in CF was related to patient genotype; those homozygozous or heterozygous for delta F508 having a significantly increased IP compared with patients with unidentified genotypes, who had IP values within the normal range.