Steatohepatitis/Metabolic Liver Disease

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Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease†

  1. Luca Miele1,
  2. Venanzio Valenza2,‡,
  3. Giuseppe La Torre3,‡,
  4. Massimo Montalto1,‡,
  5. Giovanni Cammarota1,
  6. Riccardo Ricci4,
  7. Roberta Mascianà1,
  8. Alessandra Forgione1,
  9. Maria L. Gabrieli1,
  10. Germano Perotti2,
  11. Fabio M. Vecchio4,
  12. Gianlodovico Rapaccini1,
  13. Giovanni Gasbarrini1,
  14. Chris P. Day5,§,
  15. Antonio Grieco1,§,¶,*

Article first published online: 23 JAN 2009

DOI: 10.1002/hep.22848

Issue

Hepatology

Hepatology

Volume 49, Issue 6, pages 1877–1887, June 2009

Additional Information

How to Cite

Miele, L., Valenza, V., La Torre, G., Montalto, M., Cammarota, G., Ricci, R., Mascianà, R., Forgione, A., Gabrieli, M. L., Perotti, G., Vecchio, F. M., Rapaccini, G., Gasbarrini, G., Day, C. P. and Grieco, A. (2009), Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology, 49: 1877–1887. doi: 10.1002/hep.22848

Author Information

  1. 1

    Institute of Internal Medicine, Catholic University of Rome, Rome, Italy

  2. 2

    Institute of Nuclear Medicine, Catholic University of Rome, Rome, Italy

  3. 3

    Institute of Public Health—Biostatistic Unit, Catholic University of Rome, Rome, Italy

  4. 4

    Institute of Pathology, Catholic University of Rome, Rome, Italy

  5. 5

    Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, UK

  1. ‡

    These authors contributed equally to this work.

  2. §

    These authors share senior authorship.

  3. fax: (39)-(0)6-35502775.

*Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia “Agostino Gemelli” Istituto di Medicina Interna, Largo Agostino Gemelli 8 - 00168 Rome, Italy

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    These authors contributed equally to this work.

  3. §

    These authors share senior authorship.

  4. fax: (39)-(0)6-35502775.

Publication History

  1. Issue published online: 28 MAY 2009
  2. Article first published online: 23 JAN 2009
  3. Accepted manuscript online: 23 JAN 2009 12:00AM EST
  4. Manuscript Accepted: 13 JAN 2009
  5. Manuscript Received: 16 SEP 2008

Funded by

  • Cofin MIUR - Università Cattolica del Sacro Cuore. Grant Number: “Linea D.1” 2004
  • Cofin MIUR, Università Cattolica del Sacro Cuore and “Istituto Toniolo Research Prize”. Grant Number: “Giovani Ricercatori” 2002

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Abstract

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 51Cr-ethylene diamine tetraacetate (51Cr-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. (HEPATOLOGY 2009.)

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