Skip to main content

Advertisement

SpringerLink
Log in

The effect of Saccharomyces boulardii on reducing irinotecan-induced intestinal mucositis and diarrhea

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

To investigate the efficiency of Saccharomyces boulardii on irinotecan-induced mucosal damage and diarrhea in rats, fifty rats were randomized into three groups with 20 rats in two study groups and 10 rats in the control group. Control group did not receive any treatment. Irinotecan (60 mg/kg) alone was administered intravenously once a day for four consecutive days to the rats of Group A. Throughout the experiment, Group B rats were additionally given Saccharomyces boulardii (800 mg/kg) for 3 days before administration of irinotecan and 7 days throughout the experiment. Delayed diarrhea was more severe in Group A than Group B (P = 0.009). The weight loss was 34.7 ± 3.8 mg for Group A, while it was 17.4 ± 1.7 mg for Group B (P < 0.001). Findings of mucositis most clearly appeared in the jejunum. Regarding edema (P = 0.003), leukocyte migration (P = 0.038), and inflammation (P = 0.006) significant recovery was detected in the mucosa of rats receiving Saccharomyces boulardii. Villous thickness was significantly greater in Group A than Group B (P < 0.001). The results indicate that Saccharomyces boulardii provided significant improvement in irinotecan-induced diarrhea and mucositis.

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. Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst (Bethesda). 1994;86:836–42. doi:10.1093/jnci/86.11.836.

    Article  CAS  Google Scholar 

  2. Douillard JY, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for colorectal cancer: a multicenter randomized trial. Lancet. 2000;355:1041–7. doi:10.1016/S0140-6736(00)02034-1.

    Article  PubMed  CAS  Google Scholar 

  3. Park SH, et al. Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer. Ann Oncol. 2008;19:729–33. doi:10.1093/annonc/mdm502.

    Article  PubMed  CAS  Google Scholar 

  4. Hanna N, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006;24:2038–43. doi:10.1200/JCO.2005.04.8595.

    Article  PubMed  CAS  Google Scholar 

  5. Muggia FM, Blessing JA, McGehee R, Monk BJ. Cisplatin and irinotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2004;94:483–7. doi:10.1016/j.ygyno.2004.05.018.

    Article  PubMed  CAS  Google Scholar 

  6. Ribrag V, et al. Phase II trial of irinotecan (CPT-11) in relapsed or refractory non-Hodgkin’s lymphomas. Leuk Lymphoma. 2003;44:1529–33. doi:10.1080/1042819031000099643.

    Article  PubMed  CAS  Google Scholar 

  7. Stringer AM, et al. Chemotherapy-induced mucositis: the role of gastrointestinal microflora and mucins in the luminal environment. J Support Oncol. 2007;5:259–67.

    PubMed  CAS  Google Scholar 

  8. Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DM. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol. 2003;18:1095–100. doi:10.1046/j.1440-1746.2003.03136.x.

    Article  PubMed  CAS  Google Scholar 

  9. Buts JP. Twenty-five years of research on Saccharomyces boulardii trophic effects: updates and perspectives. Dig Dis Sci. 2008 (in press).

  10. Surawicz CM, et al. Prevention of antibiotic associated diarrhoea by Saccharomyces boulardii: a prospective study. Gastroenterology. 1989;96:981–8.

    PubMed  CAS  Google Scholar 

  11. McFarland LV, et al. Prevention of ß–lactam associated diarrhoea by Saccharomyces boulardii compared with placebo. Am J Gastroenterol. 1995;90:439–48.

    PubMed  CAS  Google Scholar 

  12. McFarland LV, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994;271:1913–8. doi:10.1001/jama.271.24.1913.

    Article  PubMed  CAS  Google Scholar 

  13. Surawicz CM, et al. The search for a better treatment for Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis. 2000;31:1012–7. doi:10.1086/318130.

    Article  PubMed  CAS  Google Scholar 

  14. Buts JP, Corthier G, Delm’ee M. Saccharomyces boulardii for Clostridium difficile-associated enterocolopathies in infants. J Pediatr Gastroenterol Nutr. 1993;16:1497–504. doi:10.1097/00005176-199305000-00013.

    Google Scholar 

  15. Höchter W, Chase D, Hegenhoff G. Saccharomyces boulardii in treatment of acute adult diarrhoea efficacy and tolerance of treatment. Münch Med Wochenschr. 1990;132:188–92.

    Google Scholar 

  16. Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prevention of traveler’s diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Forstchr Med. 1993;111:152–6.

    CAS  Google Scholar 

  17. Bleichner G, Bléhaut H, Mentec H, Moyse D. Sacchromyces boulardii prevents diarrhoea in critically ill tube-fed patients. A multicenter, randomized, double-blind-placebo-controlled trial. Intensive Care Med. 1997;23:517–23. doi:10.1007/s001340050367.

    Article  PubMed  CAS  Google Scholar 

  18. Saint-Marc T, Bl’ehaut H, Musial C, Touraine JL. Efficacit’e de Saccharomyces boulardii dans le traitement des diarrh’ees du SIDA. Am Med Int. 1991;142:64–5.

    CAS  Google Scholar 

  19. Guslandi M, Mezzi G, Sorghi M, Testoni PA. Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci. 2000;45:1462–4. doi:10.1023/A:1005588911207.

    Article  PubMed  CAS  Google Scholar 

  20. Guslandi M, Giollo P, Testoni PA. A pilot trial of Saccharomyces boulardii in ulcerative colitis. Eur J Gastroenterol Hepatol. 2003;15:697–8. doi:10.1097/00042737-200306000-00017.

    Article  PubMed  Google Scholar 

  21. Pothoulakis C, et al. Saccharomyces boulardii inhibits Clostridium difficile toxin. A binding and enterotoxicity in rat ileum. Gastroenterology. 1993;104:1108–15.

    PubMed  CAS  Google Scholar 

  22. Czerucka D, Roux I, Rampal P. Saccharomyces boulardii inhibits secretagogue-mediated adenosine 3′,5′-cyclic monophosphate induction in intestinal cells. Gastroenterology. 1994;106:65–72.

    PubMed  CAS  Google Scholar 

  23. Czerucka D, Rampal P. Effect of Saccharomyces boulardii on cAMP- and Ca2+-dependent Cl-secretion in T84 cells. Dig Dis Sci. 1994;44:2359–68. doi:10.1023/A:1026689628136.

    Article  Google Scholar 

  24. Czerucka D, Dahan S, Mograbi B, Rossi B, Rampal P. Saccharomyces boulardii preserves the barrier function and modulates the transduction pathway induced in enteropathogenic Escherichia coli infected T84 cells. Infect Immun. 2000;68:5998–6004. doi:10.1128/IAI.68.10.5998-6004.2000.

    Article  PubMed  CAS  Google Scholar 

  25. Dahan S, et al. Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli induced signalling pathways in T84 cells. Infect Immun. 2003;71:766–73. doi:10.1128/IAI.71.2.766-773.2003.

    Article  PubMed  CAS  Google Scholar 

  26. Dalmasso G, et al. Saccharomyces boulardii prevents TNFa-induced apoptosis in EHEC-infected T84 cells. Res Microbiol. 2006;157:456–66. doi:10.1016/j.resmic.2005.11.007.

    Article  PubMed  CAS  Google Scholar 

  27. Qamar A, et al. Saccharomyces boulardii stimulates intestinal immunoglobulin. A immune response to Clostridium difficile toxin A in mice. Infect Immun. 2001;69:2762–5. doi:10.1128/IAI.69.4.2762-2765.2001.

    Article  PubMed  CAS  Google Scholar 

  28. Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in CB-17 scid mice. Int Immunol. 1993;5:1461–71. doi:10.1093/intimm/5.11.1461.

    Article  PubMed  CAS  Google Scholar 

  29. Lee SK, Kim YW, Chi SG, Joo YS, Kim HJ. The effect of Saccharomyces boulardii on human colon cells and inflammation in rats with trinitrobenzene sulfonic acid-induced colitis. Dig Dis Sci. 2008 (in press).

  30. Sougioultzis S, et al. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression. Biochem Biophys Res Commun. 2006;34:69–76. doi:10.1016/j.bbrc.2006.02.080.

    Article  CAS  Google Scholar 

  31. Buts JP, De Keyser N. Effects of Saccharomyces boulardii on intestinal mucosa. Dig Dis Sci. 2006;51:1485–92. doi:10.1007/s10620-005-9016-x.

    Article  PubMed  Google Scholar 

  32. Takasuna K, et al. Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea. Cancer Chemother Pharmacol. 2006;58:494–503. doi:10.1007/s00280-006-0187-8.

    Article  PubMed  CAS  Google Scholar 

  33. Logan RM, et al. Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol. 2008;62:33–41. doi:10.1007/s00280-007-0570-0.

    Article  PubMed  CAS  Google Scholar 

  34. Gibson RJ, Keefe DM. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer. 2006;14:890–900. doi:10.1007/s00520-006-0040-y.

    Article  PubMed  Google Scholar 

  35. Takasuna K, et al. Involvement of β-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res. 1996;56:3752–7.

    PubMed  CAS  Google Scholar 

  36. Kehrer DF, et al. Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res. 2001;7:1136–41.

    PubMed  CAS  Google Scholar 

  37. Dalmasso G, et al. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology. 2006;131:1812–25. doi:10.1053/j.gastro.2006.10.001.

    Article  PubMed  CAS  Google Scholar 

  38. Buts JP, Bernasconi P, Van Craynest MP, Maldague P, De Meyer R. Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. Pediatr Res. 1986;20:192–6. doi:10.1203/00006450-198602000-00020.

    Article  PubMed  CAS  Google Scholar 

  39. Jahn HU, et al. Immunological and trophical effects of Saccharomyces boulardii on the small intestine in healthy human volunteers. Digestion. 1996;57:95–104.

    Article  PubMed  CAS  Google Scholar 

  40. Harms HK, Bertele-Harms RM, Bruer-Kleis D. Enzyme substitution therapy with the yeast Saccharomyces cerevisiae in congenital sucrase isomaltase deficiency. N Engl J Med. 1987;316:1306–9.

    PubMed  CAS  Google Scholar 

  41. Buts JP, De Keyser N, Stilmant C, Sokal E, Marandi S. Saccharomyces boulardii enhances N-terminal peptide hydrolysis in suckling rat small intestine by endoluminal release of a zinc binding metalloprotease. Pediatr Res. 2002;51:528–34. doi:10.1203/00006450-200204000-00021.

    Article  PubMed  CAS  Google Scholar 

  42. Buts JP, et al. Saccharomyces boulardii upgrades cellular adaptation after proximal enterectomy in rats. Gut. 1999;45:89–96.

    Article  PubMed  CAS  Google Scholar 

  43. Baum B, Liebler-Tenorio EM, Enss ML, Pohlenz JF, Breves G. Saccharomyces boulardii and Bacillus cereus var. Toyoi influence the morphology and the mucins of the intestine of pigs. Z Gastroenterol. 2002;40:277–84. doi:10.1055/s-2002-30116.

    Article  PubMed  CAS  Google Scholar 

  44. De Preter V, et al. Effect of dietary intervention with different pre- and pro-biotics on intestinal bacterial enzyme activities. Eur J Clin Nutr. 2008;62:225–31. doi:10.1038/sj.ejcn.1602706.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey

    Atakan Sezer

  2. Department of Pathology, Faculty of Medicine, Trakya University, Edirne, Turkey

    Ufuk Usta

  3. Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne, Turkey

    Irfan Cicin

  4. Department of Medical Oncology, Elazig Training Hospital, Elazig, 23200, Turkey

    Irfan Cicin

Authors
  1. Atakan Sezer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ufuk Usta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irfan Cicin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irfan Cicin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sezer, A., Usta, U. & Cicin, I. The effect of Saccharomyces boulardii on reducing irinotecan-induced intestinal mucositis and diarrhea. Med Oncol 26, 350–357 (2009). https://doi.org/10.1007/s12032-008-9128-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-008-9128-1

Keywords

Search

Navigation