Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.
BACKGROUND
Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).


OBJECTIVE
To compare the prevalence of SIBO and its relationships to LPS receptor levels and systemic cytokines in NASH patients and healthy control subjects.


METHODS
Eighteen NASH patients (eight males) and 16 age-matched and gender-matched healthy volunteers were studied. SIBO was assessed by the lactulose breath hydrogen test (LHBT), plasma lipopolysaccharide binding protein (LBP) levels by ELISA, and expression (as a percentage) of TLR-2 and 4 on CD14-positive cells by flow cytometry. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were measured in plasma.


RESULTS
SIBO was more common in NASH patients than control subjects (77.78% vs. 31.25%; P < 0.0001). LBP levels and TLR-2 expression were similar in both groups, TLR-4/MD-2 expression on CD14 positive cells was higher among NASH patients: expression, mean ± SEM, NASH vs. control: 20.95 ± 2.91% vs. 12.73 ± 2.29%, P < 0.05. Among the examined cytokines, only IL-8 levels were significantly higher in patients than control (P = 0.04) and correlated positively with TLR-4 expression (r = 0.5123, P = 0.036).


CONCLUSIONS
NASH patients have a higher prevalence of small intestinal bacterial overgrowth which is associated with enhanced expression of TLR-4 and release of IL-8. SIBO may have an important role in NASH through interactions with TLR-4 and induction of the pro-inflammatory cytokine, IL-8.
Alimentary Pharmabiotic Centre, Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland.
Ahmed Abu
AA
Shanab
Paul
P
Scully
Orla
O
Crosbie
Martin
M
Buckley
Liam
L
O'Mahony
Fergus
F
Shanahan
Sanaa
S
Gazareen
Eileen
E
Murphy
Eamonn M M
EM
Quigley
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001944:Breath Tests; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000382:microbiology*; D007792:Lactulose / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016209:Interleukin-8; D007792:Lactulose; D008562:Membrane Glycoproteins; D051197:Toll-Like Receptor 4; D000099231:Lipopolysaccharide-Binding Protein; C495345:TLR4 protein, human