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Digestive Diseases and Sciences

, Volume 56, Issue 5, pp 1524–1534 | Cite as

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

  • Ahmed Abu Shanab
  • Paul Scully
  • Orla Crosbie
  • Martin Buckley
  • Liam O’Mahony
  • Fergus Shanahan
  • Sanaa Gazareen
  • Eileen Murphy
  • Eamonn M. M. QuigleyEmail author
Original Article

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.

Keywords

Nonalcoholic steatohepatitis Small intestinal bacterial overgrowth Microbiota Lipopolysaccharide Toll-like receptor 4 Interleukin 8 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ahmed Abu Shanab
    • 1
  • Paul Scully
    • 1
  • Orla Crosbie
    • 2
  • Martin Buckley
    • 3
  • Liam O’Mahony
    • 4
  • Fergus Shanahan
    • 1
  • Sanaa Gazareen
    • 5
  • Eileen Murphy
    • 1
  • Eamonn M. M. Quigley
    • 1
    • 6
    Email author
  1. 1.Alimentary Pharmabiotic Centre, Department of MedicineUniversity College Cork, National University of IrelandCorkIreland
  2. 2.Gastroenterology and HepatologyCork University HospitalCorkIreland
  3. 3.GastroenterologyMercy University HospitalCorkIreland
  4. 4.Swiss Institute for Allergy and Asthma ResearchDavosSwitzerland
  5. 5.General Medicine/Endocrinology, Faculty of MedicineMenoufia UniversityShebin El KomEgypt
  6. 6.Cork University HospitalCorkIreland

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