Duodenal biopsies of HIV-infected patients with diarrhoea exhibit epithelial barrier defects but no active secretion

Objectives: To characterize diarrhoeal mechanisms in HIV-infected patients, epithelial transport and barrier function of the duodenal mucosa was investigated in vitro. Patients: Twenty-one HIV-seropositive patients (13 asymptomatic and eight with diarrhoea) and 12 controls from an urban referral-based tertiary care centre in Berlin who underwent duodenoscopy. Methods: A new miniaturized Ussing chamber allowed measurements on duodenal forceps biopsies. Epithelial barrier function was characterized by alternating current impedance analysis, which allows differentiation of epithelial and subepithelial resistance and by H-3-lactulose and H-3-mannitol flux measurements. Na+-glucose cotransport was quantified as phlorizin-sensitive short circuit current (I-SC) and active ion secretion by baseline and bumetanide-sensitive I-SC. Results: Duodenal biopsies from asymptomatic HIV-infected patients were no different from controls, whereas biopsies from HIV-infected patients with diarrhoea showed a decrease in epithelial resistance from 21.2 +/- 1.9 to 12.9 +/- 1.3 Omega cm(2) (P < 0.01). Concomitantly, mucosal-to-serosal lactulose flux increased from 0.29 +/- 0.02 to 0.40 +/- 0.03 mu mol (hcm(2)) (P < 0.01). Phlorizin-sensitive I-SC indicating Na+-glucose cotransport, as well as baseline and bumetanide-sensitive I-SC indicating active electrogenic chloride secretion were not different between the three groups. Conclusions: A miniaturized Ussing device was developed for electrophysiological investigations of duodenal forceps biopsies, which allowed characterization of active ion transport mechanisms and epithelial barrier function. Duodenum of HIV-infected patients with diarrhoea showed no evidence for active ion secretion or Na+-glucose malabsorption, but showed an impaired epithelial barrier function, which could contribute to diarrhoea by a leak flux mechanism.