INTESTINAL INFECTION

Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum

Hanno Troeger¹, Hans-Joerg Epple¹, Thomas Schneider¹, Ulrich Wahnschaffe¹, Reiner Ullrich¹, Gerd-Dieter Burchard³, Tomas Jelinek⁴, Martin Zeitz¹, Michael Fromm², Joerg-Dieter Schulzke¹

¹ Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité, Berlin, Germany
² Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Berlin, Germany
³ Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
⁴ Berlin Center For Travel & Tropical Medicine, Berlin, Germany

Correspondence to:
Professor Dr J-D Schulzke
Campus Benjamin Franklin, Charité, Medizinische Klinik I, Gastroenterology, Infectious Diseases and Rheumatology, 12200 Berlin, Germany; joerg.schulzke{at}charite.de

Background: Giardia lamblia causes infection of the small intestine, which leads to malabsorption and chronic diarrhoea.

Aim: To characterise the inherent pathomechanisms of G lamblia infection.

Methods: Duodenal biopsy specimens from 13 patients with chronic giardiasis and from controls were obtained endoscopically. Short-circuit current (I_SC) and mannitol fluxes were measured in miniaturised Ussing chambers. Epithelial and subepithelial resistances were determined by impedance spectroscopy. Mucosal morphometry was performed and tight junction proteins were characterised by immunoblotting. Apoptotic ratio was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining.

Results: In giardiasis, mucosal surface area per unit serosa area was decreased to 75% (3%) of control, as a result of which epithelial resistance should increase. Instead, epithelial resistance of giardiasis biopsy specimens was decreased (19 (2) vs 25 (2) cm²; p<0.05) whereas mannitol flux was not significantly altered (140 (27) vs 105 (16) nmol/h/cm²). As structural correlate, reduced claudin 1 expression and increased epithelial apoptosis were detected. Furthermore, basal I_SC increased from 191 (20) in control to 261 (12) µA/h/cm² in giardiasis. The bumetanide-sensitive portion of I_SC in giardiasis was also increased (51 (5) vs 20 (9) µA/h/cm² in control; p<0.05). Finally, phlorizin-sensitive Na⁺–glucose symport was reduced in patients with giardiasis (121 (9) vs 83 (14) µA/h/cm²).

Conclusions: G lamblia infection causes epithelial barrier dysfunction owing to down regulation of the tight junction protein claudin 1 and increased epithelial apoptoses. Na⁺-dependent D-glucose absorption is impaired and active electrogenic anion secretion is activated. Thus, the mechanisms of diarrhoea in human chronic giardiasis comprise leak flux, malabsorptive and secretory components.

Abbreviations: IEL, intraepithelial lymphocytes; TUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling; I_sc, short-circuit current

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