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The gut microbiota—a clinical perspective on lessons learned

Nature Reviews Gastroenterology & Hepatology volume 9, pages 609–614 (2012)Cite this article

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Abstract

Once considered obscure and largely ignored by microbiologists, the human microbiota has moved centre-stage in biology. The gut microbiota is now a focus of disparate research disciplines, with its contributions to health and disease ready for translation to clinical medicine. The changing composition of the microbiota is linked with changes in human behaviour and the rising prevalence of immunoallergic and metabolic disorders. The microbiota is both a target for drug therapy and a repository for drug discovery. Its secrets promise the realization of personalized medicine and nutrition, and will change and improve conventional dietary management.

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Figure 1: Migration and disease risk.
Figure 2: Lifestyle, microbiota and disease.
Figure 3: A signalling internet
Figure 4: The sensory conundrum—friend or foe? The distinction between a harmless commensal and a potential pathogen occurs at different levels.

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References

  1. Venter, J. C. A Life Decoded. 3 (Penguin, Allen Lane, London, 2007).

    Google Scholar 

  2. Clemente, J. C., Ursell, L. K., Parfrey, L. W. & Knight, R. The impact of the gut microbiota on human health: an integrative view. Cell 148, 1258–1270 (2012).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Shanahan, F. The gut microbiota in 2011: Translating the microbiota to medicine. Nat. Rev. Gastroenterol. Hepatol. 9, 72–74 (2012).

    Article  Google Scholar 

  5. Bernstein, C. N. & Shanahan, F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 57, 1185–1191 (2008).

    Article  Google Scholar 

  6. Hviid, A., Svanström, H. & Frisch, M. Antibiotic use in inflammatory bowel diseases in childhood. Gut 60, 49–54 (2011).

    Article  Google Scholar 

  7. Shaw, S. Y., Blanchard, J. F. & Bernstein, C. N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am. J. Gastroenterol. 105, 2687–2692 (2010).

    Article  Google Scholar 

  8. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L. & Gordon, J. I. Human nutrition, the gut microbiome and the immune system. Nature 474, 327–336 (2011).

    Article  CAS  Google Scholar 

  9. Shoda, R., Matsueda, K., Yamato, S. & Umeda, N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am. J. Clin. Nutr. 63, 741–745 (1996).

    Article  CAS  Google Scholar 

  10. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).

    Article  CAS  Google Scholar 

  11. Brandl, K. et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804–807 (2008).

    Article  CAS  Google Scholar 

  12. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).

    Article  CAS  Google Scholar 

  13. Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745–757 (2011).

    Article  CAS  Google Scholar 

  14. Shulzhenko, N. et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat. Med. 17, 1585–1593 (2011).

    Article  CAS  Google Scholar 

  15. Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17, 179–188 (2011).

    Article  CAS  Google Scholar 

  16. Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).

    Article  CAS  Google Scholar 

  17. Wall, R. et al. Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am. J. Clin. Nutr. 89, 1389–1401 (2009).

    Article  Google Scholar 

  18. Murphy, E. F. et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut http://dx.doi.org/10.1136/gutjnl-2011-300705.

  19. Round, J. L. et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332, 974–977 (2011).

    Article  CAS  Google Scholar 

  20. Franchi, L. et al. NLRC-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol. 13, 449–456 (2012).

    Article  CAS  Google Scholar 

  21. Blander, J. M. & Sander, L. E. Beyond pattern recognition: five immune checkpoints for scaling the microbial threat. Nat. Rev. Immunol. 12, 215–225 (2012).

    Article  CAS  Google Scholar 

  22. Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).

    Article  CAS  Google Scholar 

  23. Lewis, K. Recover the lost art of drug discovery. Nature 485, 439–440 (2012).

    Article  CAS  Google Scholar 

  24. Rea, M. C. et al. Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4639–4644 (2011).

    Article  CAS  Google Scholar 

  25. Kelly, C. P. & LaMont, J. T. Clostridium difficile—more difficult than ever. N. Engl. J. Med. 359, 1932–1940 (2008).

    Article  CAS  Google Scholar 

  26. Im, G. Y. et al. The appendix may protect against Clostridium difficile recurrence. Clin. Gastroenterol. Hepatol. 9, 1072–1077 (2011).

    Article  Google Scholar 

  27. Hamilton, M. J., Weingarden, A. R., Sadowsky, M. J. & Khoruts, A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am. J. Gastroenerol. 107, 761–767 (2012).

    Article  Google Scholar 

  28. Shanahan, F. Probiotics in perspective. Gastroenterology 139, 1808–1812 (2010).

    Article  Google Scholar 

  29. Benezra, A., DeStefano, J. & Gordan, J. I. Anthropology of microbes. Proc. Natl Acad. Sci. USA 109, 6378–6381 (2012).

    Article  CAS  Google Scholar 

  30. Cadwell, K. et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141, 1135–1145 (2010).

    Article  CAS  Google Scholar 

  31. Kuss, S. K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011).

    Article  CAS  Google Scholar 

  32. Virgin, H. V. & Todd, J. A. Metagenomics and personalised medicine. Cell 147, 44–56 (2011).

    Article  CAS  Google Scholar 

  33. Macho Fernandez, E. et al. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 60, 1050–1059 (2011).

    Article  Google Scholar 

  34. Yan, F. & Polk, D. B. Characterization of a probiotic-derived soluble protein which reveals a mechanism of preventive and treatment effects of probiotics on intestinal inflammatory diseases. Gut Microbes 3, 25–28 (2012).

    Article  Google Scholar 

  35. Takiishi, T. et al. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice. J. Clin. Invest. 122, 1717–1725 (2012).

    Article  CAS  Google Scholar 

  36. Hamady, Z. Z. et al. Treatment of colitis with a commensal gut bacterium engineered to secrete human TGF-β1 under control of dietary zylan 1. Inflamm. Bowel Dis. 17, 1925–1935 (2011).

    Article  Google Scholar 

  37. Shanahan, F. Gut microbes: from bugs to drugs. Am. J. Gastroenterol. 105, 275–279 (2010).

    Article  Google Scholar 

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Acknowledgements

F. Shanahan is supported, in part, by Science Foundation Ireland, in the form of a centre grant: the Alimentary Pharmabiotic Centre.

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  1. Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Biosciences Building, College Road, Cork, Ireland

    Fergus Shanahan

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Competing interests

F. Shanahan has been a consultant for and received grant/research support from Alimentary Health, GlaxoSmithKline and Procter & Gamble. He is also a stock holder and patent holder with Alimentary Health.

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Shanahan, F. The gut microbiota—a clinical perspective on lessons learned. Nat Rev Gastroenterol Hepatol 9, 609–614 (2012). https://doi.org/10.1038/nrgastro.2012.145

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