Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease.
The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut-derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy-proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of (51)Cr-ethylene diamine tetraacetate ((51)Cr-EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 (ZO-1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH.


CONCLUSIONS
Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition.
Miele
Luca
L
Institute of Internal Medicine, Catholic University of Rome, Rome, Italy.
Valenza
Venanzio
V
La Torre
Giuseppe
G
Montalto
Massimo
M
Cammarota
Giovanni
G
Ricci
Riccardo
R
Mascianà
Roberta
R
Forgione
Alessandra
A
Gabrieli
Maria L
ML
Perotti
Germano
G
Vecchio
Fabio M
FM
Rapaccini
Gianlodovico
G
Gasbarrini
Giovanni
G
Day
Chris P
CP
Grieco
Antonio
A
D000328:Adult; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D019108:Tight Junctions