Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution

Nature Reviews Microbiology volume 11, pages 277–284 (2013)Cite this article

Subjects

Abstract

Hundreds of bacterial species make up the mammalian intestinal microbiota. Following perturbations by antibiotics, diet, immune deficiency or infection, this ecosystem can shift to a state of dysbiosis. This can involve overgrowth (blooming) of otherwise under-represented or potentially harmful bacteria (for example, pathobionts). Here, we present evidence suggesting that dysbiosis fuels horizontal gene transfer between members of this ecosystem, facilitating the transfer of virulence and antibiotic resistance genes and thereby promoting pathogen evolution.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mechanisms of horizontal gene transfer and enteric pathogen evolution.
Figure 2: Perturbation-induced destabilization and stabilization of intestinal ecosystems.

Similar content being viewed by others

References

  1. Berg, R. D. The indigenous gastrointestinal microflora. Trends Microbiol. 4, 430–435 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  3. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nature Rev. Genet. 13, 260–270 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Sharon, I. et al. Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res. 23, 111–120 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4554–4561 (2011).

    Article  PubMed  Google Scholar 

  9. Walker, A. W. et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5, 220–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Kelly, B. G., Vespermann, A. & Bolton, D. J. Gene transfer events and their occurrence in selected environments. Food Chem. Toxicol. 47, 978–983 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Stecher, B. et al. Salmonella enterica serovar Typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biol. 5, 2177–2189 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Barman, M. et al. Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect. Immun. 76, 907–915 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Exp. Med. 209, 1445–1456 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Stecher, B. et al. Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proc. Natl Acad. Sci. USA 109, 1269–1274 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Doucet-Populaire, F., Trieu-Cuot, P., Dosbaa, I., Andremont, A. & Courvalin, P. Inducible transfer of conjugative transposon Tn1545 from Enterococcus faecalis to Listeria monocytogenes in the digestive tracts of gnotobiotic mice. Antimicrob. Agents Chemother. 35, 185–187 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jones, B. V., Sun, F. & Marchesi, J. R. Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome. BMC Genomics 11, 46 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dagan, T., Artzy-Randrup, Y. & Martin, W. Modular networks and cumulative impact of lateral transfer in prokaryote genome evolution. Proc. Natl Acad. Sci. USA 105, 10039–10044 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Llosa, M., Schroder, G. & Dehio, C. New perspectives into bacterial DNA transfer to human cells. Trends Microbiol. 20, 355–359 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Claverys, J. P., Prudhomme, M. & Martin, B. Induction of competence regulons as a general response to stress in gram-positive bacteria. Annu. Rev. Microbiol. 60, 451–475 (2006).

    Article  CAS  PubMed  Google Scholar 

  21. Dorer, M. S., Fero, J. & Salama, N. R. DNA damage triggers genetic exchange in Helicobacter pylori. PLoS Pathog. 6, e1001026 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Meibom, K. L., Blokesch, M., Dolganov, N. A., Wu, C. Y. & Schoolnik, G. K. Chitin induces natural competence in Vibrio cholerae. Science 310, 1824–1827 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Mirold, S. et al. Isolation of a temperate bacteriophage encoding the type III effector protein SopE from an epidemic Salmonella typhimurium strain. Proc. Natl Acad. Sci. USA 96, 9845–9850 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Waldor, M. K. & Friedman, D. I. Phage regulatory circuits and virulence gene expression. Curr. Opin. Microbiol. 8, 459–465 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Brussow, H., Canchaya, C. & Hardt, W. D. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68, 560–602 (2004).

    PubMed  PubMed Central  Google Scholar 

  26. Waldor, M. K. & Mekalanos, J. J. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272, 1910–1914 (1996).

    Article  CAS  PubMed  Google Scholar 

  27. Duerkop, B. A., Clements, C. V., Rollins, D., Rodrigues, J. L. & Hooper, L. V. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl Acad. Sci. USA 109, 17621–17626 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Canchaya, C., Fournous, G., Chibani-Chennoufi, S., Dillmann, M. L. & Brussow, H. Phage as agents of lateral gene transfer. Curr. Opin. Microbiol. 6, 417–424 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Rey, F. E. et al. Dissecting the in vivo metabolic potential of two human gut acetogens. J. Biol. Chem. 285, 22082–22090 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brown Kav, A. et al. Insights into the bovine rumen plasmidome. Proc. Natl Acad. Sci. USA 109, 5452–5457 (2012).

    Article  PubMed  Google Scholar 

  31. Frost, L. S., Leplae, R., Summers, A. O. & Toussaint, A. Mobile genetic elements: the agents of open source evolution. Nature Rev. Microbiol. 3, 722–732 (2005).

    Article  CAS  Google Scholar 

  32. Stotzky, G. & Babich, H. Survival of, and genetic transfer by, genetically engineered bacteria in natural environments. Adv. Appl. Microbiol. 31, 93–138 (1986).

    Article  CAS  PubMed  Google Scholar 

  33. Sommer, M. O., Dantas, G. & Church, G. M. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325, 1128–1131 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Salyers, A. A., Gupta, A. & Wang, Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol. 12, 412–416 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Frye, J. G. et al. Related antimicrobial resistance genes detected in different bacterial species co-isolated from swine fecal samples. Foodborne Pathog. Dis. 8, 663–679 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. Aminov, I. R. in Horizontal Gene Transfer in Microorganisms (ed. Francino, M. P.) 93–130 (Caister Academic, 2012).

    Google Scholar 

  37. Dionisio, F., Matic, I., Radman, M., Rodrigues, O. R. & Taddei, F. Plasmids spread very fast in heterogeneous bacterial communities. Genetics 162, 1525–1532 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Peterson, G., Kumar, A., Gart, E. & Narayanan, S. Catecholamines increase conjugative gene transfer between enteric bacteria. Microb. Pathog. 51, 1–8 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Whitman, W. B., Coleman, D. C. & Wiebe, W. J. Prokaryotes: the unseen majority. Proc. Natl Acad. Sci. USA 95, 6578–6583 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Matsuo, J. et al. Ciliates rapidly enhance the frequency of conjugation between Escherichia coli strains through bacterial accumulation in vesicles. Res. Microbiol. 161, 711–719 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Crippen, T. L. & Poole, T. L. Conjugative transfer of plasmid-located antibiotic resistance genes within the gastrointestinal tract of lesser mealworm larvae, Alphitobius diaperinus (Coleoptera: Tenebrionidae). Foodborne Pathog. Dis. 6, 907–915 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Hinnebusch, B. J., Rosso, M. L., Schwan, T. G. & Carniel, E. High-frequency conjugative transfer of antibiotic resistance genes to Yersinia pestis in the flea midgut. Mol. Microbiol. 46, 349–354 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Salyers, A. A. Gene transfer in the mammalian intestinal tract. Curr. Opin. Biotechnol. 4, 294–298 (1993).

    Article  CAS  PubMed  Google Scholar 

  44. Sears, C. L. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin. Microbiol. Rev. 22, 349–369 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hehemann, J. H. et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Hehemann, J. H., Kelly, A. G., Pudlo, N. A., Martens, E. C. & Boraston, A. B. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proc. Natl Acad. Sci. USA 109, 19786–19791 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lupp, C. et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2, 119–129 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Lawley, T. D. et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect. Immun. 77, 3661–3669 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wohlgemuth, S., Haller, D., Blaut, M. & Loh, G. Reduced microbial diversity and high numbers of one single Escherichia coli strain in the intestine of colitic mice. Environ. Microbiol. 11, 1562–1571 (2009).

    Article  PubMed  Google Scholar 

  50. Carvalho, F. A. et al. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12, 139–152 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Winter, S. E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Stecher, B. & Hardt, W. D. Mechanisms controlling pathogen colonization of the gut. Curr. Opin. Microbiol. 14, 82–91 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Stecher, B. et al. Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog. 6, e1000711 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mason, T. G. & Richardson, G. Escherichia coli and the human gut: some ecological considerations. J. Appl. Bacteriol. 51, 1–16 (1981).

    Article  CAS  PubMed  Google Scholar 

  55. Rasko, D. A. et al. The pangenome structure of Escherichia coli: comparative genomic analysis of E. coli commensal and pathogenic isolates. J. Bacteriol. 190, 6881–6893 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ohnishi, M., Kurokawa, K. & Hayashi, T. Diversification of Escherichia coli genomes: are bacteriophages the major contributors? Trends Microbiol. 9, 481–485 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Allen, H. K. et al. Antibiotics in feed induce prophages in swine fecal microbiomes. mBio 2, e00260-11 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Bina, J. et al. ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients. Proc. Natl Acad. Sci. USA 100, 2801–2806 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lepage, P. et al. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut 57, 424–425 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Brown, S. P., Le Chat, L. & Taddei, F. Evolution of virulence: triggering host inflammation allows invading pathogens to exclude competitors. Ecol. Lett. 11, 44–51 (2008).

    PubMed  PubMed Central  Google Scholar 

  61. Thiennimitr, P., Winter, S. E. & Baumler, A. J. Salmonella, the host and its microbiota. Curr. Opin. Microbiol. 15, 108–114 (2012).

    Article  PubMed  Google Scholar 

  62. Raffatellu, M. et al. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5, 476–486 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sorsa, L. J., Dufke, S., Heesemann, J. & Schubert, S. Characterization of an iroBCDEN gene cluster on a transmissible plasmid of uropathogenic Escherichia coli: evidence for horizontal transfer of a chromosomal virulence factor. Infect. Immun. 71, 3285–3293 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Barthel, M. et al. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect. Immun. 71, 2839–2858 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Watson, P. R., Galyov, E. E., Paulin, S. M., Jones, P. W. & Wallis, T. S. Mutation of invH, but not stn, reduces Salmonella-induced enteritis in cattle. Infect. Immun. 66, 1432–1438 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Hensel, M. et al. Analysis of the boundaries of Salmonella pathogenicity island 2 and the corresponding chromosomal region of Escherichia coli K-12. J. Bacteriol. 179, 1105–1111 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li, J. et al. Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica. Proc. Natl Acad. Sci. USA 92, 7252–7256 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ochman, H. & Groisman, E. A. Distribution of pathogenicity islands in Salmonella spp. Infect. Immun. 64, 5410–5412 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Crawford, R. W. et al. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance. PLoS Pathog. 8, e1002918 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Stelter, C. et al. Salmonella-induced mucosal lectin RegIIIβ kills competing gut microbiota. PLoS ONE 6, e20749 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jacobsen, A., Hendriksen, R. S., Aaresturp, F. M., Ussery, D. W. & Friis, C. The Salmonella enterica pan-genome. Microb. Ecol. 62, 487–504 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hardt, W. D., Urlaub, H. & Galan, J. E. A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc. Natl Acad. Sci. USA 95, 2574–2579 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mirold, S. et al. Salmonella host cell invasion emerged by acquisition of a mosaic of separate genetic elements, including Salmonella pathogenicity island 1 (SPI1), SPI5, and sopE2. J. Bacteriol. 183, 2348–2358 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hardt, W. D., Chen, L. M., Schuebel, K. E., Bustelo, X. R. & Galan, J. E. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93, 815–826 (1998).

    Article  CAS  PubMed  Google Scholar 

  75. Hapfelmeier, S. et al. Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice. Infect. Immun. 72, 795–809 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Muller, A. J. et al. The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. Cell Host Microbe 6, 125–136 (2009).

    Article  CAS  PubMed  Google Scholar 

  77. Lopez, C. A. et al. Phage-mediated acquisition of a type III secreted effector protein boosts growth of Salmonella by nitrate respiration. mBio 3, e00143-12 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Winter, S. E. et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 467, 426–429 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Thiennimitr, P. et al. Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota. Proc. Natl Acad. Sci. USA 108, 17480–17485 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Garrett, W. S. et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131, 33–45 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Garrett, W. S. et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8, 292–300 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jernberg, C., Lofmark, S., Edlund, C. & Jansson, J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156, 3216–3223 (2010).

    Article  CAS  PubMed  Google Scholar 

  83. Britton, R. A. & Young, V. B. Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance. Trends Microbiol. 20, 313–319 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hill, D. A. et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 3, 148–158 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Scott, K. P. The role of conjugative transposons in spreading antibiotic resistance between bacteria that inhabit the gastrointestinal tract. Cell. Mol. Life Sci. 59, 2071–2082 (2002).

    Article  CAS  PubMed  Google Scholar 

  86. Jakobsson, H. E. et al. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS ONE 5, e9836 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Jernberg, C., Lofmark, S., Edlund, C. & Jansson, J. K. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1, 56–66 (2007).

    Article  CAS  PubMed  Google Scholar 

  88. Buffie, C. G. et al. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect. Immun. 80, 62–73 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Taur, Y. et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin. Infect. Dis. 55, 905–914 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ayres, J. S., Trinidad, N. J. & Vance, R. E. Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota. Nature Med. 18, 799–806 (2012).

    Article  CAS  PubMed  Google Scholar 

  91. Woodford, N., Turton, J. F. & Livermore, D. M. Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol. Rev. 35, 736–755 (2011).

    Article  CAS  PubMed  Google Scholar 

  92. Weinstock, G. M. Genomic approaches to studying the human microbiota. Nature 489, 250–256 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zaneveld, J. R., Nemergut, D. R. & Knight, R. Are all horizontal gene transfers created equal? Prospects for mechanism-based studies of HGT patterns. Microbiology 154, 1–15 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Kennemann, L. et al. Helicobacter pylori genome evolution during human infection. Proc. Natl Acad. Sci. USA 108, 5033–5038 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Holt, K. E. et al. High-resolution genotyping of the endemic Salmonella Typhi population during a Vi (typhoid) vaccination trial in Kolkata. PLoS Negl. Trop. Dis. 6, e1490 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Prakash, T. et al. Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of Th17 cell differentiation. Cell Host Microbe 10, 273–284 (2011).

    Article  CAS  PubMed  Google Scholar 

  97. Sczesnak, A. et al. The genome of Th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment. Cell Host Microbe 10, 260–272 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. De Paepe, M. et al. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut. PLoS Genet. 7, e1002107 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Leatham-Jensen, M. P. et al. The streptomycin-treated mouse intestine selects Escherichia coli envZ missense mutants that interact with dense and diverse intestinal microbiota. Infect. Immun. 80, 1716–1727 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Stepanauskas, R. Single cell genomics: an individual look at microbes. Curr. Opin. Microbiol. 15, 613–620 (2012).

    Article  CAS  PubMed  Google Scholar 

  101. Metchnikoff, E. The Prolongation of Life: Optimistic Studies, Revised Edition of 1907. (Heinemann,1910).

    Google Scholar 

  102. Hill, D. A. & Artis, D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu. Rev. Immunol. 28, 623–667 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Manichanh, C. et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205–211 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Moore, W. E. & Moore, L. H. Intestinal floras of populations that have a high risk of colon cancer. Appl. Environ. Microbiol. 61, 3202–3207 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Bollyky, P. L. et al. The Toll-like receptor signaling molecule Myd88 contributes to pancreatic beta-cell homeostasis in response to injury. PLoS ONE 4, e5063 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Penders, J. et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 56, 661–667 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. Hajishengallis, G., Darveau, R. P. & Curtis, M. A. The keystone-pathogen hypothesis. Nature Rev. Microbiol. 10, 717–725 (2012).

    Article  CAS  Google Scholar 

  109. Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104–108 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Arthur, J. C. et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Haag, L. M. et al. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice. PLoS ONE 7, e35988 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Barnich, N. & Darfeuille-Michaud, A. Adherent-invasive Escherichia coli and Crohn's disease. Curr. Opin. Gastroenterol. 23, 16–20 (2007).

    Article  PubMed  Google Scholar 

  113. Chow, J. & Mazmanian, S. K. A pathobiont of the microbiota balances host colonization and intestinal inflammation. Cell Host Microbe 7, 265–276 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Arboleya, S. et al. Establishment and development of intestinal microbiota in preterm neonates. FEMS Microbiol. Ecol. 79, 763–772 (2012).

    Article  CAS  PubMed  Google Scholar 

  115. Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A. & Brown, P. O. Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ventura, M., Turroni, F., Motherway, M. O., MacSharry, J. & van Sinderen, D. Host–microbe interactions that facilitate gut colonization by commensal bifidobacteria. Trends Microbiol. 20, 467–476 (2012).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work in the W.D.H. laboratory is supported by the Swiss National Science foundation (SNF). Work in the B.S. laboratory is supported by the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (BMBF).

Author information

Authors and Affiliations

  1. Bärbel Stecher is at the German Centre for Infection Research and the Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9, 80336 Munich, Germany.,

    Bärbel Stecher

  2. Lisa Maier and Wolf-Dietrich Hardt are at the Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.,

    Lisa Maier & Wolf-Dietrich Hardt

Authors
  1. Bärbel Stecher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolf-Dietrich Hardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolf-Dietrich Hardt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Bärbel Stecher's homepage

Wolf-Dietrich Hardt's homepage

GEBA

Human Microbiome Project

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stecher, B., Maier, L. & Hardt, WD. 'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol 11, 277–284 (2013). https://doi.org/10.1038/nrmicro2989

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro2989

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology