Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum
- PMID: 16935925
- PMCID: PMC1856804
- DOI: 10.1136/gut.2006.100198
Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum
Abstract
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) Omega cm(2); p<0.05) whereas mannitol flux was not significantly altered (140 (27) vs 105 (16) nmol/h/cm(2)). 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) microA/h/cm(2) in giardiasis. The bumetanide-sensitive portion of I(SC) in giardiasis was also increased (51 (5) vs 20 (9) microA/h/cm(2) in control; p<0.05). Finally, phlorizin-sensitive Na(+)-glucose symport was reduced in patients with giardiasis (121 (9) vs 83 (14) microA/h/cm(2)).
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.
Conflict of interest statement
Competing interests: None.
Comment in
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Mechanisms of epithelial dysfunction in giardiasis.Gut. 2007 Mar;56(3):316-7. doi: 10.1136/gut.2006.107771. Gut. 2007. PMID: 17339241 Free PMC article. Review.
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Colonic colonisation with Giardia lamblia in a patient receiving fibrates.Gut. 2007 Nov;56(11):1639-40. Gut. 2007. PMID: 17938439 Free PMC article. No abstract available.
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