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Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8

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Abstract

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).

Aim

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).

Conclusion

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Alimentary Pharmabiotic Centre, Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland

    Ahmed Abu Shanab, Paul Scully, Fergus Shanahan, Eileen Murphy & Eamonn M. M. Quigley

  2. Gastroenterology and Hepatology, Cork University Hospital, Cork, Ireland

    Orla Crosbie

  3. Gastroenterology, Mercy University Hospital, Cork, Ireland

    Martin Buckley

  4. Swiss Institute for Allergy and Asthma Research, Ober Strasse 22, 7270, Davos, Switzerland

    Liam O’Mahony

  5. General Medicine/Endocrinology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt

    Sanaa Gazareen

  6. Cork University Hospital, Cork, Ireland

    Eamonn M. M. Quigley

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  1. Ahmed Abu Shanab
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Shanab, A.A., Scully, P., Crosbie, O. et al. Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8. Dig Dis Sci 56, 1524–1534 (2011). https://doi.org/10.1007/s10620-010-1447-3

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  • DOI: https://doi.org/10.1007/s10620-010-1447-3

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