Skip to main content
SpringerLink
Log in

Oral Administration of Saccharomyces boulardii Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats via Reducing Intestinal Permeability and Modulating Gut Microbial Composition

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

To investigate the effects of orally administrated Saccharomyces boulardii (S. boulardii) on the progress of carbon tetrachloride (CCl4)-induced liver fibrosis, 34 male Wistar rats were randomly divided into four experimental groups including the control group (n = 8), the cirrhotic group (n = 10), the preventive group (n = 8), and the treatment group (n = 8). Results showed that the liver expression levels of collagen, type I, alpha 1 (Col1A1), alpha smooth muscle actin (αSMA), transforming growth factor beta (TGF-β) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) increased significantly in cirrhotic rats compared with control and decreased by S. boulardii administration. Treatment of S. boulardii also attenuated the increased endotoxin levels and pro-inflammatory cytokines in CCl4-treated rats. And, these were associated with the changes of intestinal permeability and fecal microbial composition. Our study suggested that oral administration of S. boulardii can promote the liver function of CCl4-treated rats, and the preventive treatment of this probiotic yeast may decelerate the progress of liver fibrosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. El Bialy, S.A., K.F. El Kader, and M.B. El-Ashmawy. 2011. Current progress in antifibrotics. Current Medicinal Chemistry 18: 3082–3092.

    Article  PubMed  Google Scholar 

  2. Friedman, S.L. 2004. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nature Clinical Practice Gastroenterology and Hepatology 1: 98–105.

    Article  PubMed  Google Scholar 

  3. Friedman, S.L., F.J. Roll, J. Boyles, et al. 1985. Hepatic lipocytes: the principal collagen-producing cells of normal rat liver. Proceedings of the National Academy of Sciences of the United States of America 82: 8681–8685.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Friedman, S.L., and M.B. Bansal. 2006. Reversal of hepatic fibrosis—fact or fantasy? Hepatology 43: S82–S88.

    Article  CAS  PubMed  Google Scholar 

  5. Chen, Y., F. Yang, H. Lu, B. Wang, et al. 2011. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54: 562–572.

    Article  PubMed  Google Scholar 

  6. Cesaro, C., A. Tiso, A. Del Prete, R. Cariello, et al. 2011. Gut microbiota and probiotics in chronic liver diseases. Digestive and Liver Disease 43: 431–438.

    Article  PubMed  Google Scholar 

  7. Guerrero Hernandez, I., A. Torre Delgadillo, F. Vargas Vorackova, et al. 2008. Intestinal flora, probiotics, and cirrhosis. Annals of Hepatology 7: 120–124.

    PubMed  Google Scholar 

  8. Zhang, W., Y. Gu, Y. Chen, et al. 2010. Intestinal flora imbalance results in altered bacterial translocation and liver function in rats with experimental cirrhosis. European Journal of Gastroenterology and Hepatology 22: 1481–1486.

    PubMed  Google Scholar 

  9. Graff, S., J.C. Chaumeil, P. Boy, R. Lai-Kuen, et al. 2008. Influence of pH conditions on the viability of Saccharomyces boulardii yeast. The Journal of General and Applied Microbiology 54: 221–227.

    Article  CAS  PubMed  Google Scholar 

  10. Edwards-Ingram, L., P. Gitsham, N. Burton, et al. 2007. Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae. Applied and Environmental Microbiology 73: 2458–2467.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kelesidis, T., and C. Pothoulakis. 2012. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therapeutic Advances in Gastroenterology 5: 111–125.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Can, M., B.A. Besirbellioglu, I.Y. Avci, et al. 2006. Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research 12: 19–22.

    Google Scholar 

  13. McFarland, L.V. 2010. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World Journal of Gastroenterology 16: 2202–2222.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Schneider, S.M., F. Girard-Pipau, J. Filippi, et al. 2005. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World Journal of Gastroenterology 11: 6165–6169.

    CAS  PubMed  Google Scholar 

  15. Leonel, A.J., and J.I. Alvarez-Leite. 2012. Butyrate: implications for intestinal function. Current Opinion in Clinical Nutrition and Metabolic Care 15: 474–479.

    Article  CAS  PubMed  Google Scholar 

  16. Everard, A., S. Matamoros, L. Geurts, et al. 2014. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. mBio 5(3): e01011–e01014.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Clawson, G.A. 1989. Mechanisms of carbon tetrachloride hepatotoxicity. Pathology and Immunopathology Research 8: 104–112.

    Article  CAS  PubMed  Google Scholar 

  18. Sanchez, E., J. C. Nieto, A. Boullosa, et al. 2014. VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon tetrachloride-induced cirrhosis. Liver International Article first published online: 12 MAY 2014 doi: 10.1111/liv.12566.

  19. D'Argenio, G., R. Cariello, C. Tuccillo, et al. 2013. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage? Liver International 33: 687–697.

    Article  PubMed  Google Scholar 

  20. Affò, S., O. Morales-Ibanez, D. Rodrigo-Torres, et al. 2014. CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis. Gut Article first published online: 12 AUG 2014 doi:10.1136/gutjnl-2013-306098.

  21. Yagi, K., S. Matsuoka, A.W. Linnane, et al. 1981. Plasma lipid peroxide levels in an urbanized Micronesian population—Nauru. Journal of Nutritional Science and Vitaminology 27: 425–428.

    Article  CAS  PubMed  Google Scholar 

  22. Satoh, K., S. Takamatsu, S. Sakuta, et al. 1981. Augmented malondialdehyde production by platelets from patients with cerebrovascular disorders. Japanese Circulation Journal 45: 1335–1341.

    Article  CAS  PubMed  Google Scholar 

  23. Poyrazoglu, O.K., I.H. Bahcecioglu, H. Ataseven, et al. 2008. Effect of unfiltered coffee on carbon tetrachloride-induced liver injury in rats. Inflammation 31: 408–413.

    Article  CAS  PubMed  Google Scholar 

  24. Lee, I.H., A. Dinudom, A. Sanchez-Perez, et al. 2007. Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. The Journal of Biological Chemistry 282: 29866–29873.

    Article  CAS  PubMed  Google Scholar 

  25. Joossens, M., G. Huys, M. Cnockaert, et al. 2011. Dysbiosis of the fecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut 60: 631–637.

    Article  PubMed  Google Scholar 

  26. Liu, Y., T. Zhou, D. Crowley, et al. 2012. Decline in topsoil microbial quotient, fungal abundance and C utilization efficiency of rice paddies under heavy metal pollution across South China. PLoS ONE 7: e38858.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Penders, J., C. Thijs, C. Vink, et al. 2006. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118: 511–521.

    Article  PubMed  Google Scholar 

  28. Salzman, N.H., H. Kuiechun, D. Haribhai, et al. 2010. Enteric defensins are essential regulators of intestinal microbial ecology. Nature Immunology 11: 76–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Bartosch, S., A. Fite, G.T. Macfarlane, et al. 2004. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Applied and Environmental Microbiology 70: 3575–3581.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Wiest, R., F. Chen, G. Cadelina, et al. 2003. Effect of Lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension. Digestive Diseases and Sciences 48: 1136–1141.

    Article  CAS  PubMed  Google Scholar 

  31. Soriano, G., E. Sanchez, C. Guarner, et al. 2012. Lactobacillus johnsonii La1 without antioxidants does not decrease bacterial translocation in rats with carbon tetrachloride-induced cirrhosis. Journal of Hepatology 57: 1395–1396.

    Article  PubMed  Google Scholar 

  32. Rincon, D., J. Vaquero, A. Hernando, et al. 2014. Oral probiotic vsl#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites. Liver International Article first published online: 4 APR 2014 doi: 10.1111/liv.12539.

  33. Dapito, D.H., A. Mencin, G.Y. Gwak, et al. 2012. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21(4): 504–516.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Chan, C.C., S.J. Hwang, F.Y. Lee, et al. 1997. Prognostic value of plasma endotoxin levels in patients with cirrhosis. Scandinavian Journal of Gastroenterology 32: 942–946.

    Article  CAS  PubMed  Google Scholar 

  35. Rietschel, E.T., T. Kirikae, F.U. Schade, et al. 1994. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB Journal 8: 217–225.

    CAS  PubMed  Google Scholar 

  36. Raetz, C.R., and C. Whitfield. 2002. Lipopolysaccharide endotoxins. Annual Review of Biochemistry 71: 635–700.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Schnabl, B., and D.A. Brenner. 2014. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146: 1513–1524.

    Article  CAS  PubMed  Google Scholar 

  38. Gomez-Hurtado, I., A. Santacruz, G. Peiro, et al. 2011. Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis. PLoS ONE 6: e23037.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Plummer, J.L., C.J. Ossowicz, C. Whibley, et al. 2000. Influence of intestinal flora on the development of fibrosis and cirrhosis in a rat model. Journal of Gastroenterology and Hepatology 15: 1307–1311.

    CAS  PubMed  Google Scholar 

  40. Riordan, S.M., and R. Williams. 2006. The intestinal flora and bacterial infection in cirrhosis. Journal of Hepatology 45: 744–757.

    Article  PubMed  Google Scholar 

  41. Llovet, J.M., R. Bartoli, F. March, et al. 1998. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. Journal of Hepatology 28: 307–313.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Key Project of the National Twelfth-Five Year Research Program of China (2012BAI35B02), the National HighTechnology Research and Development Progran (863 Program) of China (2014AA022200), and the Specialized Research Fund for the Doctoral Program of Higher Education of China (20132105120012).

Author information

Authors and Affiliations

  1. Department of Microecology, School of Basic Medical Science, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Lvshunkou District, 116044, Dalian, China

    Ming Li, Lin Zhu, Ao Xie & Jieli Yuan

Authors
  1. Ming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ao Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jieli Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jieli Yuan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Zhu, L., Xie, A. et al. Oral Administration of Saccharomyces boulardii Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats via Reducing Intestinal Permeability and Modulating Gut Microbial Composition. Inflammation 38, 170–179 (2015). https://doi.org/10.1007/s10753-014-0019-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-0019-7

KEY WORDS

Search

Navigation