PTU-036 Environmental Enteropathy: Imaging The Cellular Basis Of Disrupted Barrier Function

Abstract

INTRODUCTION: Environmental enteropathy (EE), originally termed tropical enteropathy, is very common in overcrowded living conditions in developing countries. It predisposes to growth failure in the young, and probably to poor performance of oral vaccines. By permitting microbial translocation it probably contributes to insidious systemic immune activation. In order to understand the impairment of barrier function in EE, we performed confocal laser endomicroscopy (CLE) in 57 healthy volunteers from a poor community in Lusaka, Zambia. AIMS & METHODS: These asymptomatic volunteers were drawn from a community in which we have been conducting studies for 15 years. On day 1 a 3 hour lactulose: mannitol permeability and zinc absorption test was performed. On day 2 CLE of the duodenal mucosa was performed with diazepam/pethidine sedation and 5-10ml 2% intravenous fluorescein, and images collected for 10 minutes exactly (mean number of images analysed 135, SD57). Biopsies were subsequently taken to analyse villous morphology and markers of bacterial translocation and inflammation. RESULTS: In the first 57 volunteers (40 female, 17 male) studied, a wide range of villous architectural patterns was observed from leaf-like to convolutions. Similarly, a wide range of barrier abnormalities was observed, with some volunteers showing severe fluorescein leakage within one minute of fluorescein injection. Epithelial breaks, particularly multicellular breaks (microerosions), were strongly correlated with the rate of fluorescein efflux (Spearman's rho 0.92; P<0.0001). The number of plumes was almost as strongly correlated (rho=0.69; p=0.0004). Fluorescein leakage and epithelial barrier defects were not correlated with villous architectural change (rho=0.01: p=0.96), suggesting that villous remodelling and barrier defects are differentially determined. Fluorescein plumes were correlated with serum CD163, a marker of Kupffer cell activation, but only in HIV seropositive individuals (rho=0.76; P,0.05). CONCLUSION: CLE permits imaging of small intestinal epithelial barrier defects and suggests that cellular breaches are major routes of intestinal permeability but independent of villous architecture.