Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum.
BACKGROUND
Giardia lamblia causes infection of the small intestine, which leads to malabsorption and chronic diarrhoea.


OBJECTIVE
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.
Troeger
Hanno
H
Campus Benjamin Franklin, Charité, Medizinische Klinik I, Gastroenterology, Infectious Diseases and Rheumatology, 12200 Berlin, Germany.
Epple
Hans-Joerg
HJ
Schneider
Thomas
T
Wahnschaffe
Ulrich
U
Ullrich
Reiner
R
Burchard
Gerd-Dieter
GD
Jelinek
Tomas
T
Zeitz
Martin
M
Fromm
Michael
M
Schulzke
Joerg-Dieter
JD
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D001693:Biological Transport, Active; D001706:Biopsy; D002908:Chronic Disease; D062445:Claudin-1; D004386:Duodenum / Q000473:pathology / Q000503:physiopathology*; D016829:Giardia lamblia; D005873:Giardiasis / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007408:Intestinal Absorption; D007411:Intestinal Diseases, Parasitic / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D008286:Malabsorption Syndromes / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D010539:Permeability; D019108:Tight Junctions / Q000378:metabolism
C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins