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Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1, 2-dimethylhydrazine-induced rat model

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Abstract

Probiotics have been suggested as a prophylactic measure in colon cancer. The aim of this study was to investigate the impact of Lactobacillus salivarius Ren (Ren) in modulating colonic microbiota structure and colon cancer incidence in a rat model after injection with 1,2-dimethyl hydrazine (DMH). The results indicated that oral administration of Ren could effectively suppress DMH-induced colonic carcinogenesis. A significant decrease in cancer incidence (87.5% to 25%) was detected in rats fed with a dose of 5 × 1010 CFU/kg bodyweight per day. Using denaturing gradient gel electrophoresis and Real-time PCR combined with multivariate statistical methods, we demonstrated that injection with DMH significantly altered the rat gut microbiota, while Ren counteracted these DMH-induced adverse effects and promoted reversion of the gut microbiota close to the healthy state. Tvalue biplots followed by band sequencing identified 21 bacterial strains as critical variables affected by DMH and Ren. Injection of DMH significantly increased the amount of Ruminococcus species (sp.) and Clostridiales bacteria, as well as decreasing the Prevotella sp. Administration of Ren reduced the amount of Ruminococcus sp., Clostridiales bacteria, and Bacteroides dorei, and increased the amount of Prevotella. Real-time PCR results were consistent with the results derived by t-value biplots. These findings suggested that Ren is a potential agent for colon cancer prevention. In conclusion, the results in the present study suggest a potential therapeutic approach based on the modulation of intestinal microflora by probiotics may be beneficial in the prevention of colorectal carcinogenesis.

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References

  • Arthur, J.C., Gharaibeh, R.Z., Uronis, J.M., Perez-Chanona, E., Sha, W., Tomkovich, S., Muhlbauer, M., Fodor, A.A., and Jobin, C. 2013. VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci. Rep. 3, 2868.

    Article  PubMed Central  PubMed  Google Scholar 

  • Arthur, J.C., Perez-Chanona, E., Muhlbauer, M., Tomkovich, S., Uronis, J.M., Fan, T.J., Campbell, B.J., Abujamel, T., Dogan, B., Rogers, A.B., et al. 2012. Intestinal inflammation targets cancer- inducing activity of the microbiota. Science 338, 120–123.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Camp, J.G., Kanther, M., Semova, I., and Rawls, J.F. 2009. Patterns and scales in gastrointestinal microbial ecology. Gastroenterology 136, 1989–2002.

    Article  PubMed  Google Scholar 

  • Dicksved, J., Lindberg, M., Rosenquist, M., Enroth, H., Jansson, J.K., and Engstrand, L. 2009. Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. J. Med. Microbiol. 58, 509–516.

    Article  CAS  PubMed  Google Scholar 

  • Dove, W.F., Clipson, L., Gould, K.A., Luongo, C., Marshall, D.J., Moser, A.R., Newton, M.A., and Jacoby, R.F. 1997. Intestinal neoplasia in the ApcMin mouse: Independence from the microbial and natural killer (beige locus) status. Cancer Res. 57, 812–814.

    CAS  PubMed  Google Scholar 

  • Geier, M.S., Butler, R.N., and Howarth, G.S. 2006. Probiotics, prebiotics and synbiotics- A role in chemoprevention for colorectal cancer? Cancer Biol. Ther. 5, 1265–1269.

    Article  CAS  PubMed  Google Scholar 

  • Greer, J.B. and O’Keefe, S.J. 2011. Microbial induction of immunity, inflammation, and cancer. Front Physiol. 1, 168.

    Article  PubMed Central  PubMed  Google Scholar 

  • Guarner, F. and Malagelada, J.R. 2003. Gut flora in health and disease. Lancet 361, 512–519.

    Article  PubMed  Google Scholar 

  • Hamer, H.M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F.J., and Brummer, R.J. 2008. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27, 104–119.

    Article  CAS  PubMed  Google Scholar 

  • Janczyk, P., Pieper, R., Smidt, H., and Souffrant, W.B. 2010. Effect of alginate and inulin on intestinal microbial ecology of weanling pigs reared under different husbandry conditions. FEMS Microbiol. Ecol. 72, 132–142.

    Article  CAS  PubMed  Google Scholar 

  • Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., and Forman, D. 2011. Global cancer statistics. CA Cancer J. Clin. 61, 69–90.

    Article  PubMed  Google Scholar 

  • Kado, S., Uchida, K., Funabashi, H., Iwata, S., Nagata, Y., Ando, M., Onoue, M., Matsuoka, Y., Ohwaki, M., and Morotomi, M. 2001. Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. Cancer Res. 61, 2395–2398.

    CAS  PubMed  Google Scholar 

  • Kumar, M., Kumar, A., Nagpal, R., Mohania, D., Behare, P., Verma, V., Kumar, P., Poddar, D., Aggarwal, P.K., Henry, C.J.K., et al. 2010. Cancer-preventing attributes of probiotics: an update. Int. J. Food Sci. Nutr. 61, 473–496.

    Article  CAS  PubMed  Google Scholar 

  • Lepš, J. and Šmilauer, P. 2003. Multivariate analysis of ecological data using CANOCO. Cambridge University Press, Cambridge, UK.

    Book  Google Scholar 

  • Licht, T.R., Hansen, M., Poulsen, M., and Dragsted, L.O. 2006. Dietary carbohydrate source influences molecular fingerprints of the rat faecal microbiota. BMC Microbiol. 6 98.

    Article  PubMed Central  PubMed  Google Scholar 

  • Matsuki, T., Watanabe, K., Fujimoto, J., Takada, T., and 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 Central  CAS  PubMed  Google Scholar 

  • Moore, W.E.C. and Moore, L.H. 1995. Intestinal floras of populations that have a high-risk of colon-cancer. Appl. Environ. Microbiol. 61, 3202–3207.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nagengast, F.M., Grubben, M.J., and van Munster, I.P. 1995. Role of bile acids in colorectal carcinogenesis. Eur. J. Cancer 31A, 1067–1070.

    Article  CAS  PubMed  Google Scholar 

  • Nicholson, J.K., Holmes, E., and Wilson, I.D. 2005. Gut microorganisms, mammalian metabolism and personalized health care. Nat. Rev. Microbiol. 3, 431–438.

    Article  CAS  PubMed  Google Scholar 

  • Ohigashi, S., Sudo, K., Kobayashi, D., Takahashi, O., Takahashi, T., Asahara, T., Nomoto, K., and Onodera, H. 2013. Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. Dig. Dis. Sci. 58, 1717–1726.

    Article  CAS  PubMed  Google Scholar 

  • Onoue, M., Kado, S., Sakaitani, Y., Uchida, K., and Morotomi, M. 1997. Specific species of intestinal bacteria influence the induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats. Cancer Lett. 113, 179–186.

    Article  CAS  PubMed  Google Scholar 

  • Piazzi, G., D’Argenio, G., Prossomariti, A., Lembo, V., Mazzone, G., Candela, M., Biagi, E., Brigidi, P., Vitaglione, P., Fogliano, V., et al. 2014. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota. Int. J. Cancer 135, 2004–2013.

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti, C.J., Neto, E.D., and Simpson, A.J.G. 1994. Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. Biotechniques 17, 914–921.

    CAS  PubMed  Google Scholar 

  • Sobhani, I., Tap, J., Roudot-Thoraval, F., Roperch, J.P., Letulle, S., Langella, P., Corthier, G., Jeanne, T.V.N., and Furet, J.P. 2011. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 6, e16393.

    Article  Google Scholar 

  • Tannock, G.W., Munro, K., Bibiloni, R., Simon, M.A., Hargreaves, P., Gopal, P., Harmsen, H., and Welling, G. 2004. Impact of consumption of oligosaccharide-containing biscuits on the fecal microbiota of humans. Appl. Environ. Microbiol. 70, 2129–2136.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thompson-Chagoyan, O.C., Maldonado, J., and Gil, A. 2007. Colonization and impact of disease and other factors on intestinal microbiota. Dig. Dis. Sci. 52, 2069–2077.

    Article  PubMed  Google Scholar 

  • Torres, E.A.F.D., Garbelotti, M.L., and Neto, J.M.M. 2006. The application of hierarchical clusters analysis to the study of the composition of foods. Food Chem. 99, 622–629.

    Article  CAS  Google Scholar 

  • Uronis, J.M., Muhlbauer, M., Herfarth, H.H., Rubinas, T.C., Jones, G.S., and Jobin, C. 2009. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 4, e6026.

    Article  Google Scholar 

  • Wei, H., Dong, L., Wang, T.T., Zhang, M.H., Hua, W.Y., Zhang, C.H., Pang, X.Y., Chen, M.J., Su, M.M., Qiu, Y.P., et al. 2010. Structural shifts of gut microbiota as surrogate endpoints for monitoring host health changes induced by carcinogen exposure. FEMS Microbiol. Ecol. 73, 577–586.

    CAS  PubMed  Google Scholar 

  • White, I.R., Pickford, R., Wood, J., Skehel, J.M., Gangadharan, B., and Cutler, P. 2004. A statistical comparison of silver and SYPRO Ruby staining for proteomic analysis. Electrophoresis 25, 3048–3054.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, M., Qiao, X.W., Zhao, L., Jiang, L., and Ren, F.Z. 2011. Lactobacillus salivarius REN counteracted unfavorable 4-nitroquinoline- 1-oxide-induced changes in colonic microflora of rats. J. Microbiol. 49, 877–883.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, M., Wang, F., Jiang, L., Liu, R.H., Zhang, L., Lei, X.G., Li, J.Y., Jiang, J.L., Guo, H.Y., Fang, B., et al. 2013. Lactobacillus salivarius REN inhibits rat oral cancer induced by 4-nitroquioline 1-oxide. Cancer Prev. Res. 6, 686–694.

    Article  CAS  Google Scholar 

  • Zhu, J., Zhu, C., Ge, S., Zhang, M., Jiang, L., Cui, J., and Ren, F. 2014. Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model. J. Appl. Microbiol. 117, 208–216.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Fazheng Ren.

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Zhang, M., Fan, X., Fang, B. et al. Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1, 2-dimethylhydrazine-induced rat model. J Microbiol. 53, 398–405 (2015). https://doi.org/10.1007/s12275-015-5046-z

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  • DOI: https://doi.org/10.1007/s12275-015-5046-z

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