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. 2001 Feb;48(2):206–211. doi: 10.1136/gut.48.2.206

The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis

A Wigg 1, I Roberts-Thomson 1, R Dymock 1, P McCarthy 1, R Grose 1, A Cummins 1
PMCID: PMC1728215  PMID: 11156641

Abstract

BACKGROUND—Small intestinal bacterial overgrowth may contribute to the development of non-alcoholic steatohepatitis, perhaps by increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products.
AIMS—To investigate the prevalence of small intestinal bacterial overgrowth, increased intestinal permeability, elevated endotoxin, and tumour necrosis factor α (TNF-α) levels in patients with non-alcoholic steatohepatitis and in control subjects.
PATIENTS AND METHODS—Twenty two patients with non-alcoholic steatohepatitis and 23 control subjects were studied. Small intestinal bacterial overgrowth was assessed by a combined 14C-D-xylose and lactulose breath test. Intestinal permeability was assessed by a dual lactulose-rhamnose sugar test. Serum endotoxin levels were determined using the limulus amoebocyte lysate assay and TNF-α levels using an ELISA.
RESULTS—Small intestinal bacterial overgrowth was present in 50% of patients with non-alcoholic steatosis and 22% of control subjects (p=0.048). Mean TNF-α levels in non-alcoholic steatohepatitis patients and control subjects were 14.2 and 7.5 pg/ml, respectively (p=0.001). Intestinal permeability and serum endotoxin levels were similar in the two groups.
CONCLUSIONS—Patients with non-alcoholic steatohepatitis have a higher prevalence of small intestinal bacterial overgrowth, as assessed by the 14C-D-xylose-lactulose breath test, and higher TNF-α levels in comparison with control subjects. This is not accompanied by increased intestinal permeability or elevated endotoxin levels.


Keywords: non-alcoholic steatohepatitis; small intestinal bacterial overgrowth; intestinal permeability; endotoxin; tumour necrosis factor α

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Selected References

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  1. Ashkenazi A., Marsters S. A., Capon D. J., Chamow S. M., Figari I. S., Pennica D., Goeddel D. V., Palladino M. A., Smith D. H. Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10535–10539. doi: 10.1073/pnas.88.23.10535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Freund H. R. Abnormalities of liver function and hepatic damage associated with total parenteral nutrition. Nutrition. 1991 Jan-Feb;7(1):1–6. [PubMed] [Google Scholar]
  3. James O., Day C. Non-alcoholic steatohepatitis: another disease of affluence. Lancet. 1999 May 15;353(9165):1634–1636. doi: 10.1016/S0140-6736(99)00163-4. [DOI] [PubMed] [Google Scholar]
  4. Kim W. R., Poterucha J. J., Porayko M. K., Dickson E. R., Steers J. L., Wiesner R. H. Recurrence of nonalcoholic steatohepatitis following liver transplantation. Transplantation. 1996 Dec 27;62(12):1802–1805. doi: 10.1097/00007890-199612270-00021. [DOI] [PubMed] [Google Scholar]
  5. King C. E., Toskes P. P., Spivey J. C., Lorenz E., Welkos S. Detection of small intestine bacterial overgrowth by means of a 14C-D-xylose breath test. Gastroenterology. 1979 Jul;77(1):75–82. [PubMed] [Google Scholar]
  6. Lewis S. J., Young G., Mann M., Franco S., O'Keefe S. J. Improvement in specificity of [14C]d-xylose breath test for bacterial overgrowth. Dig Dis Sci. 1997 Aug;42(8):1587–1592. doi: 10.1023/a:1018880524829. [DOI] [PubMed] [Google Scholar]
  7. Lichtman S. N., Keku J., Schwab J. H., Sartor R. B. Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology. 1991 Feb;100(2):513–519. doi: 10.1016/0016-5085(91)90224-9. [DOI] [PubMed] [Google Scholar]
  8. Lichtman S. N., Sartor R. B., Keku J., Schwab J. H. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990 Feb;98(2):414–423. doi: 10.1016/0016-5085(90)90833-m. [DOI] [PubMed] [Google Scholar]
  9. Miki K., Butler R., Moore D., Davidson G. Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice. Clin Chem. 1996 Jan;42(1):71–75. [PubMed] [Google Scholar]
  10. Mohler K. M., Sleath P. R., Fitzner J. N., Cerretti D. P., Alderson M., Kerwar S. S., Torrance D. S., Otten-Evans C., Greenstreet T., Weerawarna K. Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature. 1994 Jul 21;370(6486):218–220. doi: 10.1038/370218a0. [DOI] [PubMed] [Google Scholar]
  11. Nazim M., Stamp G., Hodgson H. J. Non-alcoholic steatohepatitis associated with small intestinal diverticulosis and bacterial overgrowth. Hepatogastroenterology. 1989 Oct;36(5):349–351. [PubMed] [Google Scholar]
  12. Pappo I., Bercovier H., Berry E. M., Haviv Y., Gallily R., Freund H. R. Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide. JPEN J Parenter Enteral Nutr. 1992 Nov-Dec;16(6):529–532. doi: 10.1177/0148607192016006529. [DOI] [PubMed] [Google Scholar]
  13. Tarao K., So K., Moroi T., Ikeuchi T., Suyama T. Detection of endotoxin in plasma and ascitic fluid of patients with cirrhosis: its clinical significance. Gastroenterology. 1977 Sep;73(3):539–542. [PubMed] [Google Scholar]
  14. Winkler G., Salamon F., Harmos G., Salamon D., Speer G., Szekeres O., Hajós P., Kovács M., Simon K., Cseh K. Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity. Diabetes Res Clin Pract. 1998 Dec;42(3):169–174. doi: 10.1016/s0168-8227(98)00109-0. [DOI] [PubMed] [Google Scholar]
  15. Yang S. Q., Lin H. Z., Lane M. D., Clemens M., Diehl A. M. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2557–2562. doi: 10.1073/pnas.94.6.2557. [DOI] [PMC free article] [PubMed] [Google Scholar]

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