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Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies

An Erratum to this article was published on 26 June 2010

Abstract

Purpose

Probiotics are expected to be effective in prophylaxis of infection in cancer patient, since infections in neutropenics are mainly caused by endogenous flora through the intestinal mucosa. However, the experience with the use of probiotics in immunocompromised patients is limited, and precise fecal bacteria analysis has not been reported. The aim of the study was to evaluate the effects of the enteral administration of the probiotic, Bifidobacterium breve strain Yakult, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy.

Methods

A placebo-controlled trial was performed at Juntendo University Hospital. Patients with malignancies admitted for chemotherapy (n = 42) were randomized into two groups receiving probiotic or placebo. The effects on infectious complications, natural killer cells, fecal micro flora, fecal organic acid concentrations, and fecal pH were studied.

Results

The frequency of fever and the use of intravenous antibiotics were lower in the probiotic group than the placebo group. The probiotic administration enhanced the habitation of anaerobes. Disruption of the intestinal microbiota after chemotherapy such as the increase in the population levels of Enterobacteriaceae was observed at more pronounced manner in the placebo group in comparison to the probiotic group. The concentrations of total organic acids were maintained most of the time at the normal level, which constantly maintained the pH below 7.0 only in the probiotic group.

Conclusion

These data, although based on a limited number of patients and samples, suggest that administration of B. breve strain Yakult could be an effective approach for achieving clinical benefits in immunocompromised hosts by improving their intestinal environments.

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References

  1. Schimpff SC, Young VM, Greene WH, Vermeulen GD, Moody MR, Wiernik PH (1972) Origin of infection in acute nonlymphocytic leukemia. Significance of hospital acquisition of potential pathogens. Ann Intern Med 77:707–714

    PubMed  CAS  Google Scholar 

  2. Klastersky J (1989) A review of chemoprophylaxis and therapy of bacterial infections in neutropenic patients. Diagn Microbiol Infect Dis 12:201S–207S

    Article  PubMed  CAS  Google Scholar 

  3. Marshall JC (1999) Gastrointestinal flora and its alterations in critical illness. Curr Opin Clin Nutr Metab Care 2:405–411

    Article  PubMed  CAS  Google Scholar 

  4. Guarner F, Schaafsma GJ (1998) Probiotics. Int J Food Microbiol 39:237–238

    Article  PubMed  CAS  Google Scholar 

  5. Nova E, Warnberg J, Gomez-Martinez S, Diaz LE, Romeo J, Marcos A (2007) Immunomodulatory effects of probiotics in different stages of life. Br J Nutr 98:S90–S95

    Article  PubMed  CAS  Google Scholar 

  6. Van Niel CW, Feudtner C, Garrison MM, Christakis DA (2002) Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 109:678–684

    Article  PubMed  Google Scholar 

  7. Yasui H, Ohwaki M (1991) Enhancement of immune response in Peyer’s patch cells cultured with Bifidobacterium breve. J Dairy Sci 74:1187–1195

    Article  PubMed  CAS  Google Scholar 

  8. Resta-Lenert S, Barrett KE (2003) Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 52:988–997

    Article  PubMed  CAS  Google Scholar 

  9. Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M, Yokokura T (1999) Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice. Med Microbiol Immunol 188:111–116

    Article  PubMed  CAS  Google Scholar 

  10. Aso Y, Akaza H, Kotake T, Tsukamoto T, Imai K, Naito S (1995) Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double-blind trial. The BLP study group. Eur Urol 27:104–109

    PubMed  CAS  Google Scholar 

  11. Lee JW, Shin JG, Kim EH, Kang HE, Yim IB, Kim JY et al (2004) Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum. J Vet Sci 5:41–48

    PubMed  Google Scholar 

  12. Takeda K, Okumura K (2007) Effects of a fermented milk drink containing Lactobacillus casei strain shirota on the human NK-cell activity. J Nutr 137:791S–793S

    PubMed  CAS  Google Scholar 

  13. Shida K, Suzuki T, Kiyoshima-Shibata J, Shimada S, Nanno M (2006) Essential roles of monocytes in stimulating human peripheral blood mononuclear cells with Lactobacillus casei to produce cytokines and augment natural killer cell activity. Clin Vaccine Immunol 13:997–1003

    Article  PubMed  CAS  Google Scholar 

  14. Tojo M, Oikawa T, Morikawa Y, Yamashita N, Iwata S, Satoh Y et al (1987) The effects of Bifidobacterium breve administration on Campylobacter enteritis. Acta Paediatr Jpn 29:160–167

    PubMed  CAS  Google Scholar 

  15. Hotta M, Sato Y, Iwata S, Yamashita N, Sunakawa K, Oikawa T et al (1987) Clinical effects of Bifidobacterium preparations on pediatric intractable diarrhea. Keio J Med 36:298–314

    PubMed  CAS  Google Scholar 

  16. Kanamori Y, Hashizume K, Sugiyama M, Mortomi M, Yuki N, Tanaka R (2002) A novel synbiotic therapy dramatically improved the intestinal function of a pediatric patient with laryngotracheo-esophageal cleft (LTEC) in the intensive care unit. Clin Nutr 21:527–530

    Article  PubMed  CAS  Google Scholar 

  17. Sonoike K, Mada M, Mutai M (1986) Selective agar medium for counting viable cells of bifidobacteria in fermented milk. J Food Hyg Soc Jpn 27:238–244

    Google Scholar 

  18. Matsuki T, Watanabe K, Fujimoto J, Takada T, Tanaka R (2004) Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces. Appl Environ Microbiol 70:7220–7228

    Article  PubMed  CAS  Google Scholar 

  19. Kikuchi H, Yajima T (1992) Correlation between water-holding capacity of different types of cellulose in vitro and gastrointestinal retention time in vivo of rats. J Sci Food Agric 60:139–146

    Article  CAS  Google Scholar 

  20. Mego M, Ebringer L, Drgona L, Mardiak J, Trupl J, Greksak R et al (2005) Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Pilot study phase I. Neoplasma 52:159–164

    PubMed  CAS  Google Scholar 

  21. Mego M, Koncekova R, Mikuskova E, Drgona L, Ebringer L, Demitrovicova L et al (2006) Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Phase II study. Support Care Cancer 14:285–290

    Article  PubMed  CAS  Google Scholar 

  22. D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ (2002) Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324:1361

    Article  PubMed  Google Scholar 

  23. Yasui H, Shida K, Matsuzaki T, Yokokura T (1999) Immunomodulatory function of lactic acid bacteria. Antonie Van Leeuwenhoek 76:383–389

    Article  PubMed  CAS  Google Scholar 

  24. Berg RD (1999) Bacterial translocation from the gastrointestinal tract. Adv Exp Med Biol 473:11–30

    PubMed  CAS  Google Scholar 

  25. Tancrède CH, Andremont AO (1985) Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies. J Infect Dis 152:99–103

    PubMed  Google Scholar 

  26. Asahara T, Nomoto K, Shimizu K, Watanuki M, Tanaka R (2001) Increased resistance of mice to Salmonella enterica serovar Typhimurium infection by synbiotic administration of Bifidobacteria and transgalactosylated oligosaccharides. J Appl Microbiol 91:985–996

    Article  PubMed  CAS  Google Scholar 

  27. Asahara T, Shimizu K, Nomoto K, Hamabata T, Ozawa A, Takeda Y (2004) Probiotic Bifidobacteria protect mice from lethal infection with Shiga toxin-producing Escherichia coli O157:H7. Infect Immun 72:2240–2247

    Article  PubMed  CAS  Google Scholar 

  28. Asahara T, Shimizu K, Nomoto K, Watanuki M, Tanaka R (2001) Antibacterial effect of fermented milk containing Bifidobacterium breve, Bifidobacterium bifidum and Lactobacillus acidophilus against indigenous Escherichia coli infection in mice. Microb Ecol Health Dis 13:16–24

    Article  CAS  Google Scholar 

  29. Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M et al (2003) Safety of probiotics that contain lactobacilli or bifidobacteria. Clin Infect Dis 36:775–780

    Article  PubMed  CAS  Google Scholar 

  30. De Groote MA, Frank DN, Dowell E, Glode MP, Pace NR (2005) Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 24:278–280

    Article  PubMed  Google Scholar 

  31. Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM et al (2008) Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–659

    Article  PubMed  Google Scholar 

  32. Kitajima H, Sumida Y, Tanaka R, Yuki N, Takayama H, Fujimura M (1997) Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 76:F101–F107

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We gratefully thank Enkhtuya Lkhagvadorj, MD, Lei Bian, Chongxin Wang, MD, Yukihide Chiba, MD, and Takahiro Kudo, MD for their excellent technical support. We are also grateful to Jyunya Fujimura, MD, Oto Takada, MD, and Sachi Sakaguchi, MD for their help in sampling valuable clinical specimens.

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Correspondence to Mariko Wada.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00520-010-0938-2

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Wada, M., Nagata, S., Saito, M. et al. Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies. Support Care Cancer 18, 751–759 (2010). https://doi.org/10.1007/s00520-009-0711-6

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  • DOI: https://doi.org/10.1007/s00520-009-0711-6

Keywords

  • Probiotics
  • Immunocompromised host
  • Infection prevention
  • Intestinal microflora
  • Organic acids
  • pH