Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8
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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).
To compare the prevalence of SIBO and its relationships to LPS receptor levels and systemic cytokines in NASH patients and healthy control subjects.
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.
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).
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.
KeywordsNonalcoholic steatohepatitis Small intestinal bacterial overgrowth Microbiota Lipopolysaccharide Toll-like receptor 4 Interleukin 8
Supported in part by an award to the Alimentary Pharmabiotic Centre by Science Foundation Ireland and by a scholarship to AAS from the Egyptian Government.
- 18.Pilotto A, Franceschi M, Del Favero G, et al. The effect of aging on oro-cecal transit time in normal subjects and patients with gallstone disease. Aging (Milano). 1995;7:234–237.Google Scholar
- 39.Romics L Jr, Mandrekar P, Kodys K, Velayudham A, Drechsler Y, Dolganiuc A, Szabo G. Increased lipopolysaccharide sensitivity in alcoholic fatty livers is independent of leptin deficiency and toll-like receptor 4 (TLR4) or TLR2 mRNA expression. Alcohol Clin Exp Res. 2005;9:1018–1026.Google Scholar
- 44.Thurman RG, Bradford BU, Knecht KT, et al. Endotoxin, Kupffer cells and alcoholic liver injury. In: Blum HE, Bode Ch, Bode JCh, Sartor RB (ed) Gut and the liver. Falk Symposium 100, Dordrecht, The Netherlands. Kluwer Academic Publishers Group, 1997:222–240.Google Scholar
- 45.Bode Ch, Schafer C, Bode JCh. The role of gut derived bacterial toxins (endotoxin) for the development of alcoholic liver disease in man. In: Blum HE, Bode Ch, Bode JCh, Sartor RB (ed) Gut and the liver. Falk Symposium 100, Dordrecht, The Netherlands. Kluwer Academic Publishers Group, 1997:281–298.Google Scholar
- 47.Copaci I, Micu L, Voiculescu M. The role of cytokines in non-alcoholic steatohepatitis. A review. J Gastrointest Liver Dis. 2006;15:363–373.Google Scholar
- 56.Nonalcoholic steatohepatitis clinical research network. Hepatology. 2003;37:244.Google Scholar
- 64.Bratten JR, Spanier J, Jones MP. Lactulose hydrogen breath testing (LHBT) in patients with IBS and controls: Differences in methane (CH4) but not hydrogen (H2). Am J Gastroenterol. 2006;101:S479.Google Scholar
- 65.Simon D, Borelli S, Braathen LR, Simon HU. Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-gamma. Allergy. 2002;57:431–435.PubMedGoogle Scholar
- 83.Igolnikov AC, Green RM. C3H/HEJ mice with mutations of the toll-like receptor 4 (TLR-4) are resistant to the methionine-choline deficient (MCD) diet induced non-alcoholic steatohepatitis (NASH). Hepatology. 2003;36:A404.Google Scholar
- 87.Tuncer I, Özbek H, Topal H, Uygan I. The serum levels of IL-1B, Il-6, IL-8 and TNF alpha in non alcoholic fatty liver disease. Turk J Med Sci. 2003;33:381–386.Google Scholar