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Bile salt hydrolase-mediated inhibitory effect of Bacteroides ovatus on growth of Clostridium difficile

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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Abstract

Clostridium difficile infection (CDI) is one of the most common nosocomial infections. Dysbiosis of the gut microbiota due to consumption of antibiotics is a major contributor to CDI. Recently, fecal microbiota transplantation (FMT) has been applied to treat CDI. However, FMT has important limitations including uncontrolled exposure to pathogens and standardization issues. Therefore, it is necessary to evaluate alternative treatment methods, such as bacteriotherapy, as well as the mechanism through which beneficial bacteria inhibit the growth of C. difficile. Here, we report bile acid-mediated inhibition of C. difficile by Bacteroides strains which can produce bile salt hydrolase (BSH). Bacteroides strains are not commonly used to treat CDI; however, as they comprise a large proportion of the intestinal microbiota, they can contribute to bile acid-mediated inhibition of C. difficile. The inhibitory effect on C. difficile growth increased with increasing bile acid concentration in the presence of Bacteroides ovatus SNUG 40239. Furthermore, this inhibitory effect on C. difficile growth was significantly attenuated when bile acid availability was reduced by cholestyramine, a bile acid sequestrant. The findings of this study are important due to the discovery of a new bacterial strain that in the presence of available bile acids inhibits growth of C. difficile. These results will facilitate development of novel bacteriotherapy strategies to control CDI.

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References

  • Allegretti, J.R., Kearney, S., Li, N., Bogart, E., Bullock, K., Gerber, G.K., Bry, L., Clish, C.B., Alm, E., and Korzenik, J.R. 2016. Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles. Aliment. Pharmacol. Ther. 43, 1142–1153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakken, J.S., Borody, T., Brandt, L.J., Brill, J.V., Demarco, D.C., Franzos, M.A., Kelly, C., Khoruts, A., Louie, T., Martinelli, L.P., et al. 2011. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. 9, 1044–1049.

    Article  PubMed  PubMed Central  Google Scholar 

  • Begley, M., Hill, C., and Gahan, C.G. 2006. Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 72, 1729–1738.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buffie, C.G., Bucci, V., Stein, R.R., McKenney, P.T., Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew, M., Viale, A., et al. 2014. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208.

    Article  PubMed  PubMed Central  Google Scholar 

  • Burke, K.E. and Lamont, J.T. 2014. Clostridium difficile infection: A worldwide disease. Gut Liver 8, 1–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiang, J.Y.L. 2009. Bile acids: regulation of synthesis. J. Lipid Res. 50, 1955–1966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cocolin, L., Innocente, N., Biasutti, M., and Comi, G. 2004. The late blowing in cheese: a new molecular approach based on PCR and DGGE to study the microbial ecology of the alteration process. Int. J. Food Microbiol. 90, 83–91.

    Article  CAS  PubMed  Google Scholar 

  • Geeraerts, S., Ducatelle, R., Haesebrouck, F., and Van Immerseel, F. 2015. Bacillus amyloliquefaciens as prophylactic treatment for Clostridium difficile associated disease in a mouse model. J. Gastroenterol. Hepatol. 30, 1275–1280.

    Article  CAS  PubMed  Google Scholar 

  • Gérard, P. 2013. Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens 3, 14–24.

    Article  PubMed  PubMed Central  Google Scholar 

  • Giel, J.L., Sorg, J.A., Sonenshein, A.L., and Zhu, J. 2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS One 5, e8740.

    Article  Google Scholar 

  • Jarocki, P. 2011. Molecular characterization of bile salt hydrolase from Bifidobacterium animalis subsp. lactis Bi30. J. Microbiol. Biotechnol. 21, 838–845.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.S., Han, D.S., Kim, Y.H., Kim, W.H., Kim, J.S., Kim, H.S., Kim, H.S., Park, Y.S., Song, H.J., Shin, S.J., et al. 2013. Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study. Epidemiol. Infect. 141, 189–194.

    Article  CAS  PubMed  Google Scholar 

  • Kink, J.A. and Williams, J.A. 1998. Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile-associated disease in a hamster model of infection. Infect. Immun. 66, 2018–2025.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Longo, D.L., Leffler, D.A., and Lamont, J.T. 2015. Clostridium difficile Infection. N. Engl. J. Med. 372, 1539–1548.

    Article  Google Scholar 

  • Martin, J.S.H., Monaghan, T.M., and Wilcox, M.H. 2016. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission. Nat. Rev. Gastroenterol. Hepatol. 13, 206–216.

    Article  PubMed  Google Scholar 

  • Pavlidis, P., Powell, N., Vincent, R.P., Ehrlich, D., Bjarnason, I., and Hayee, B. 2015. Systematic review: Bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence? Aliment. Pharmacol. Ther. 42, 802–817.

    Article  CAS  PubMed  Google Scholar 

  • Peláez, T., Alcalá, L., Alonso, R., Rodríguez-Créixems, M., García-Lechuz, J.M., and Bouza, E. 2002. Reassessment of clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob. Agents Chemother. 46, 1647–1650.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ridlon, J.M., Kang, D.J., and Hylemon, P.B. 2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47, 241–259.

    Article  CAS  PubMed  Google Scholar 

  • Ridlon, J., Kang, D., Hylemon, P., and Bajaj, J. 2014. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 30, 332–338.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rohlke, F. and Stollman, N. 2012. Fecal microbiota transplantation in relapsing Clostridium difficile infection. Therap. Adv. Gastroenterol. 5, 403–420.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rupnik, M., Wilcox, M.H., and Gerding, D.N. 2009. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7, 526–536.

    Article  CAS  PubMed  Google Scholar 

  • Sayin, S.I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., and Bäckhed, F. 2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235.

    Article  CAS  PubMed  Google Scholar 

  • Seekatz, A.M. and Young, V.B. 2014. Clostridium difficile and the microbiota. J. Clin. Invest. 124, 4182–4189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sekirov, I., Russell, S.L., Antunes, L.C.M., and Finlay, B.B. 2010. Gut microbiota in health and disease. Physiol. Rev. 90, 859–904.

    Article  CAS  PubMed  Google Scholar 

  • Shahinas, D., Silverman, M., Sittler, T., Chiu, C., Kim, P., Allen-Vercoe, E., Weese, S., Wong, A., Low, D.E., and Pillai, D.R. 2012. Toward an understanding of changes in diversity associated with fecal microbiome transplantation based on 16S rRNA gene deep sequencing. mBio 3, E00338–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smits, W.K., Lyras, D., Lacy, D.B., Wilcox, M.H., and Kuijper, E.J. 2016. Clostridium difficile infection. Nat. Rev. Dis. Prim. 2, 16020.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sorg, J.A. and Sonenshein, A.L. 2008. Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190, 2505–2512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorg, J.A. and Sonenshein, A.L. 2010. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol. 192, 4983–4990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, M., Ahrné, S., Jeppsson, B., and Molin, G. 2005. Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol. Ecol. 54, 219–231.

    Article  CAS  PubMed  Google Scholar 

  • Wang, Q., Euler, C.W., Delaune, A., and Fischetti, V.A. 2015. Using a novel lysin to help control Clostridium difficile infections. Antimicrob. Agents Chemother. 59, 7447–7457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wells, J.E., Williams, K.B., Whitehead, T.R., Heuman, D.M., and Hylemon, P.B. 2003. Development and application of a polymerase chain reaction assay for the detection and enumeration of bile acid 7α-dehydroxylating bacteria in human feces. Clin. Chim. Acta. 331, 127–134.

    Article  CAS  PubMed  Google Scholar 

  • Wexler, H.M. 2007. Bacteroides: The good, the bad, and the nittygritty. Clin. Microbiol. Rev. 20, 593–621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, M., McNulty, N.P., Rodionov, D.A., Khoroshkin, M.S., Griffin, N.W., Cheng, J., Latreille, P., Kerstetter, R.A., Terrapon, N., Henrissat, B., et al. 2015. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides. Science 350, aac5992.

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, 08826, Republic of Korea

    Soobin Yoon, Junsun Yu, Andrea McDowell & GwangPyo Ko

  2. KoBioLabs, Inc., Seoul, 08826, Republic of Korea

    Sung Ho Kim & GwangPyo Ko

  3. Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul, 08826, Republic of Korea

    Hyun Ju You & GwangPyo Ko

  4. Bio-MAX/N-Bio, Seoul National University, Seoul, 08826, Republic of Korea

    GwangPyo Ko

Authors
  1. Soobin Yoon
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  2. Junsun Yu
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  3. Andrea McDowell
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  4. Sung Ho Kim
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  5. Hyun Ju You
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  6. GwangPyo Ko
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Correspondence to Hyun Ju You or GwangPyo Ko.

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Yoon, S., Yu, J., McDowell, A. et al. Bile salt hydrolase-mediated inhibitory effect of Bacteroides ovatus on growth of Clostridium difficile. J Microbiol. 55, 892–899 (2017). https://doi.org/10.1007/s12275-017-7340-4

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  • DOI: https://doi.org/10.1007/s12275-017-7340-4

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