Movatterモバイル変換


[0]ホーム

URL:


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.

Advertisement

Nature Reviews Genetics
  • Review Article
  • Published:

The human microbiome: at the interface of health and disease

Nature Reviews Geneticsvolume 13pages260–270 (2012)Cite this article

Subjects

Key Points

  • The human microbiome and its relationship to disease is a new and rapidly evolving field of study.

  • The co-evolution between hosts and their microbiomes has led to cooperative interactions in metabolism and homeostasis.

  • Concepts from community ecology — such as resilience, community disturbances and extinction — are useful in understanding the microbiome.

  • New computational and statistical tools are being developed to analyse the large sequence data sets that are generated by the increasingly powerful technologies.

  • The taxonomic composition and functional characteristics of the microbiome may allow individuals to be categorized into different microbial patterns, called enterotypes, in the gastrointestinal tract. Although low-level taxonomy varies substantially among individuals, higher-level taxonomy and functional characteristics seem to be largely preserved.

  • Many factors affect the composition of the microbiome over the course of a human lifetime. These include inheritance, the mode of infant delivery, diet and age-related changes in adults.

  • The relationships between the microbiome and several human diseases are being intensively studied for conditions that include colorectal cancer, inflammatory bowel disease and immunologically mediated skin diseases.

  • Causal relationships for many of the associations between the microbiome and disease states have yet to be proven.

  • Understanding the links between the microbiome and human disease may provide prophylactic or therapeutic tools to improve human health.

Abstract

Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.

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

Access options

Access through your institution

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF

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

Figure 1: Compositional differences in the microbiome by anatomical site.
Figure 2: Conservation of bacterial genes despite taxonomic variation.
Figure 3: Acquisition of the microbiome in early life by vertical transmission, and factors modifying mother-to-child microbial transmission.

Similar content being viewed by others

References

  1. Baumann, P. & Moran, N. A. Non-cultivable microorganisms from symbiotic associations of insects and other hosts.Antonie van Leeuwenhoek72, 39–48 (1997).

    Article CAS PubMed  Google Scholar 

  2. Turnbaugh, P. J. et al. The Human Microbiome Project.Nature449, 804–810 (2007).

    Article CAS PubMed PubMed Central  Google Scholar 

  3. Ehrlich, S. D.Metagenomics of the Human Body (ed. Nelson, K. E.) 307–316 (Springer, 2011).

    Book  Google Scholar 

  4. Ravel, J. et al. Vaginal microbiome of reproductive-age women.Proc. Natl Acad. Sci. USA108, 4680–4687 (2011).This study describes vaginal microbiome differences and similarities in women of reproductive age who vary by ethnicity, and explores factors that are related to bacterial vaginosis.

    Article CAS PubMed  Google Scholar 

  5. Arumugam, M. et al. Enterotypes of the human gut microbiome.Nature473, 174–180 (2011).This paper proposes enterotype classifications that are defined by the intrinsic characteristics of the gut microbiome, and that seem to be independent of ethnic or dietary factors.

    Article CAS PubMed PubMed Central  Google Scholar 

  6. Morris, S. C. & Peel, J. S. The earliest annelids: lower Cambrian polychaetes from the Sirius Passet Lagerstatte, Peary Land, North Greenland.Acta Palaeontol. Pol.53, 135–146 (2008).

    Article  Google Scholar 

  7. Ley, R., Lozupone, C. A., Hamady, M., Knight, R. & Gordon, J. Worlds within worlds: evolution of the vertebrate gut microbiota.Nature Rev. Microbiol.6, 776–788 (2008).A review that contrasts the microbial communities in the vertebrate gut with each other and with free-living microbial communities.

    Article CAS  Google Scholar 

  8. Ochman, H. et al. Evolutionary relationships of wild hominids recapitulated by gut microbial communities.PLoS Biol.8, e1000546 (2010).

    Article PubMed PubMed Central CAS  Google Scholar 

  9. Moran, N. A., Munson, M. A., Baumann, P. & Ishikawa, H. A Molecular clock in endosymbiotic bacteria is calibrated using the insect hosts.Proc. R. Soc. Lond. B253, 167–171 (1993).

    Article  Google Scholar 

  10. Benson, A. K. et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.Proc. Natl Acad. Sci. USA107, 18933–18938 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  11. Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.Proc. Natl Acad. Sci. USA106, 3698–3703 (2009).A comparison of germ-free and normal animals, which shows that the microbiome has substantial effects on host blood metabolites, including on the metabolism of amino acids and organic acids.

    Article CAS PubMed PubMed Central  Google Scholar 

  12. Petchey, O. L., Eklof, A., Borrvall, C. & Ebenman, B. Trophically unique species are vulnerable to cascading extinction.Am. Nat.171, 568–579 (2008).

    Article PubMed  Google Scholar 

  13. Blaser, M. J. & Kirschner, D. The equilibria that allow bacterial persistence in human hosts.Nature449, 843–849 (2007).The authors of this paper propose that co-evolved bacteria in human hosts establish homeostases that conform to the principles of Nash equilibria. Understanding such equilibria may provide insight into shifts in microbial communities in health and disease.

    Article CAS PubMed  Google Scholar 

  14. Maynard Smith, J.Models in Ecology. (Cambridge Univ. Press, UK, 1974).

    Google Scholar 

  15. Blaser, M. J. Who are we? Indigenous microbes and the ecology of human diseases.EMBO Rep.7, 956–960 (2006).

    Article CAS PubMed PubMed Central  Google Scholar 

  16. Tringe, S. G. et al. Comparative metagenomics of microbial communities.Science308, 554–557 (2005).

    Article CAS PubMed  Google Scholar 

  17. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest.Nature444, 1027–1031 (2006).A seminal paper describing the ability of the gut microbiome to extract energy from dietary sources.

    Article PubMed  Google Scholar 

  18. Warnecke, F. et al. Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite.Nature450, 560–565 (2007).

    Article CAS PubMed  Google Scholar 

  19. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing.Nature464, 59–65 (2010).The authors report the identification of a library of microbial genes that are found in the human gut microbiome using high-throughput metagenomic sequencing.

    Article CAS PubMed PubMed Central  Google Scholar 

  20. Nelson, K. E. et al. A catalog of reference genomes from the human microbiome.Science328, 994–999 (2010).

    Article CAS PubMed  Google Scholar 

  21. Kuczynski, J. et al. Experimental and analytical tools for studying the human microbiome.Nature Rev. Genet.13, 47–58 (2012).

    Article CAS  Google Scholar 

  22. Greenblum, S., Turnbaugh, P. J. & Borenstein, E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.Proc. Natl Acad. Sci. USA109, 594–599 (2012).A new method of comparing metagenomic data that involves analysing metabolic networks and their associated genes to describe changes that occur in disease (such as in obesity or IBD).

    Article CAS PubMed  Google Scholar 

  23. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora.Science308, 1635–1638 (2005).

    Article PubMed PubMed Central  Google Scholar 

  24. Bogaert, D. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis.PLoS ONE6, e17035 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  25. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time.Science326, 1694–1697 (2009).This study describes temporal and topographical variations in the human microbiome at various anatomical sites.

    Article CAS PubMed PubMed Central  Google Scholar 

  26. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes.Science334, 105–108 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  27. Kuczynski, J. et al. Direct sequencing of the human microbiome readily reveals community differences.Genome Biol.11, 210 (2010).

    Article PubMed PubMed Central CAS  Google Scholar 

  28. Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation.Proc. Natl Acad. Sci. USA108, 4554–4561 (2011).This paper describes the substantial alterations that occur in the gut microbiome after exposure to antibiotics. It also highlights varied taxonomic changes among individuals.

    Article CAS PubMed  Google Scholar 

  29. Dethlefsen, L., Huse, S., Sogin, M. L. & Relman, D. A. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.PLoS Biol.6, e280 (2008).

    Article PubMed PubMed Central CAS  Google Scholar 

  30. Huse, S. M. et al. Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing.PLoS Genet.4, e1000255 (2008).

    Article PubMed PubMed Central CAS  Google Scholar 

  31. Ley, R. E. et al. Obesity alters gut microbial ecology.Proc. Natl Acad. Sci. USA102, 11070–11075 (2005).

    Article CAS PubMed PubMed Central  Google Scholar 

  32. Linz, B. et al. An African origin for the intimate association between humans andHelicobacter pylori.Nature445, 915–918 (2007).

    Article PubMed PubMed Central  Google Scholar 

  33. Douglass, J. M., Li, Y. & Tinanoff, N. Association of mutans streptococci between caregivers and their children.Pediatr. Dent.30, 375–387 (2008).

    PubMed  Google Scholar 

  34. Li, Y., Ismail, A. I., Ge, Y., Tellez, M. & Sohn, W. Similarity of bacterial populations in saliva from African-American mother-child dyads.J. Clin. Microbiol.45, 3082–3085 (2007).

    Article CAS PubMed PubMed Central  Google Scholar 

  35. Li, M. et al. Symbiotic gut microbes modulate human metabolic phenotypes.Proc. Natl Acad. Sci. USA105, 2117–2122 (2008).

    Article CAS PubMed PubMed Central  Google Scholar 

  36. McNulty, N. P. et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.Sci. Transl. Med.3, 106ra106 (2011).

    Article PubMed PubMed Central CAS  Google Scholar 

  37. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins.Nature457, 480–484 (2009).

    Article CAS PubMed  Google Scholar 

  38. Fierer, N., Hamady, M., Lauber, C. L. & Knight, R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria.Proc. Natl Acad. Sci. USA105, 17994–17999 (2008).

    Article CAS PubMed PubMed Central  Google Scholar 

  39. 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).This study describes the taxonomic developments that occur in the infant microbiome and the relationships between these changes and environmental exposures.

    Article PubMed PubMed Central CAS  Google Scholar 

  40. Blaser, M. J. & Falkow, S. What are the consequences of the disappearing human microbiota?Nature Rev. Microbiol.7, 887–894 (2009).This article proposes that our modern lifestyle has led to the extinction of certain microbes, and that their disappearance may have deleterious effects on human health.

    Article CAS  Google Scholar 

  41. Sjolund, M., Wreiber, K., Andersson, D. I., Blaser, M. J. & Engstrand, L. Long-term persistence of resistantEnterococcus species after antibiotics to eradicateHelicobacter pylori.Ann. Intern. Med.139, 483–487 (2003).

    Article PubMed  Google Scholar 

  42. Blaser, M. J. Antibiotic overuse: stop the killing of beneficial bacteria.Nature476, 393–394 (2011).

    Article CAS PubMed  Google Scholar 

  43. Evans, A. S. Causation and disease: the Henle–Koch postulates revisited.Yale J. Biol. Med.49, 175–195 (1976).

    CAS PubMed PubMed Central  Google Scholar 

  44. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans.Science332, 970–974 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  45. Huston, M. A.Biological Diversity: The Coexistence Of Species On Changing Landscapes (Cambridge Univ. Press, UK, 1994).

    Google Scholar 

  46. Kennedy, T. A. et al. Biodiversity as a barrier to ecological invasion.Nature417, 636–638 (2002).

    Article CAS PubMed  Google Scholar 

  47. Strogatz, S. H. Exploring complex networks.Nature410, 268–276 (2001).

    Article CAS PubMed  Google Scholar 

  48. Paine, R. T. Food web complexity and species diversity.Am. Nat.100, 65–75 (1966).

    Article  Google Scholar 

  49. Sole, R. V. & Montoya, J. M. Complexity and fragility in ecological networks.Proc. Biol. Sci.268, 2039–2045 (2001).

    Article CAS PubMed PubMed Central  Google Scholar 

  50. Borrvall, C. & Ebenman, B. Early onset of secondary extinctions in ecological communities following the loss of top predators.Ecol. Lett.9, 435–442 (2006).

    Article PubMed  Google Scholar 

  51. Bik, E. M. et al. Molecular analysis of the bacterial microbiota in the human stomach.Proc. Natl Acad. Sci. USA103, 732–737 (2006).

    Article CAS PubMed PubMed Central  Google Scholar 

  52. Maldonado-Contreras, A. et al. Structure of the human gastric bacterial community in relation toHelicobacter pylori status.ISME J.5, 574–579 (2011).

    Article CAS PubMed  Google Scholar 

  53. Li, Y., Caufield, P. W., Dasanayake, A. P., Wiener, H. W. & Vermund, S. H. Mode of delivery and other maternal factors influence the acquisition ofStreptococcus mutans in infants.J. Dent. Res.84, 806–811 (2005).

    Article CAS PubMed  Google Scholar 

  54. Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.Proc. Natl Acad. Sci. USA107, 11971–11975 (2010).This study shows that infants have largely undifferentiated microbiota across multiple anatomic sites immediately after birth, and that delivery mode determines which types of bacteria of the infant microbiome are the earliest colonizers.

    Article PubMed PubMed Central  Google Scholar 

  55. Savage, D. C., Dubos, R. & Schaedler, R. W. The gastrointestinal epithelium and its autochthonous bacterial flora.J. Exp. Med.127, 67–76 (1968).One of the pioneering studies of the features of the bacterial colonization of the gastrointestinal tract that occurs in early life.

    Article CAS PubMed PubMed Central  Google Scholar 

  56. Gronlund, M. M., Lehtonen, O. P., Eerola, E. & Kero, P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery.J. Pediatr. Gastroenterol. Nutr.28, 19–25 (1999).

    Article CAS PubMed  Google Scholar 

  57. Grant, B. R. & Grat, P. R. Cultural inheritance of song and its role in the evolution of Darwin's finches.Evolution50, 2471–2487 (1996).

    Article PubMed  Google Scholar 

  58. Hunt, J. & Simmons, L. W. Maternal and paternal effects on offspring phenotype in the dung beetleOnthophagus taurus.Evolution54, 936–941 (2000).

    Article CAS PubMed  Google Scholar 

  59. Raymond, J. et al. Genetic and transmission analysis ofHelicobacter pylori strains within a family.Emerg. Infect. Dis.10, 1816–1821 (2004).

    Article CAS PubMed PubMed Central  Google Scholar 

  60. Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome.Nature480, 241–244 (2011).The discovery of a large network of gene exchange that occurs in microbial communities and that allows rapid genetic information transfer to occur in the microbiome. The authors speculate that such networks have roles in specific human diseases.

    Article CAS PubMed  Google Scholar 

  61. Wirth, T. et al. Distinguishing human ethnic groups by means of sequences fromHelicobacter pylori: lessons from Ladakh.Proc. Natl Acad. Sci. USA101, 4746–4751 (2004).

    Article CAS PubMed PubMed Central  Google Scholar 

  62. Sharon, G. et al. Commensal bacteria play a role in mating preference ofDrosophila melanogaster.Proc. Natl Acad. Sci. USA107, 20051–20056 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  63. Leyden, J. J., McGinley, K. J., Holzle, E., Labows, J. N. & Kligman, A. M. The microbiology of the human axilla and its relationship to axillary odor.J. Invest. Dermatol.77, 413–416 (1981).

    Article CAS PubMed  Google Scholar 

  64. Dobzhansky, T. Further data on the variation of the Y chromosome inDrosophila pseudoobscura.Genetics22, 340–346 (1937).

    CAS PubMed PubMed Central  Google Scholar 

  65. Mayr, E.Systematics And The Origin Of Species From The Viewpoint Of A Zoologist (Columbia Univ. Press, New York, USA, 1942).

    Google Scholar 

  66. Brailsford, S. R. et al. The microflora of the erupting first permanent molar.Caries Res.39, 78–84 (2005).

    Article CAS PubMed  Google Scholar 

  67. Cephas, K. D. et al. Comparative analysis of salivary bacterial microbiome diversity in edentulous infants and their mothers or primary care givers using pyrosequencing.PLoS ONE6, e23503 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  68. Schaedler, R. W. The relationshp between the host and its intestinal microflora.Proc. Nutr. Soc.32, 41–47 (1973).

    Article CAS PubMed  Google Scholar 

  69. Jukes, T. H. Antibiotics in feeds.Science204, 8 (1979).

    Article CAS PubMed  Google Scholar 

  70. Robinson, C. J. & Young, V. B. Antibiotic administration alters the community structure of the gastrointestinal micobiota.Gut Microbes1, 279–284 (2010).

    Article PubMed PubMed Central  Google Scholar 

  71. Wlodarska, M. et al. Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbatedCitrobacter rodentium-induced colitis.Infect. Immun.79, 1536–1545 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  72. Gemmell, N. J. & Slate, J. Heterozygote advantage for fecundity.PLoS ONE1, e125 (2006).

    Article PubMed PubMed Central CAS  Google Scholar 

  73. Cauci, S. et al. Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women.J. Clin. Microbiol.40, 2147–2152 (2002).

    Article PubMed PubMed Central  Google Scholar 

  74. Osborne, N. G., Wright, R. C. & Grubin, L. Genital bacteriology: a comparative study of premenopausal women with postmenopausal women.Am. J. Obstet. Gynecol.135, 195–198 (1979).

    Article CAS PubMed  Google Scholar 

  75. Peek, R. M. Jr & Blaser, M. J.Helicobacter pylori and gastrointestinal tract adenocarcinomas.Nature Rev. Cancer2, 28–37 (2002).

    Article CAS  Google Scholar 

  76. Giannakis, M., Chen, S. L., Karam, S. M., Engstrand, L. & Gordon, J. I.Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.Proc. Natl Acad. Sci. USA105, 4358–4363 (2008).

    Article CAS PubMed PubMed Central  Google Scholar 

  77. Li, X. X. et al. Bacterial microbiota profiling in gastritis withoutHelicobacter pylori infection or non-steroidal anti-inflammatory drug use.PLoS ONE4, e7985 (2009).

    Article PubMed PubMed Central CAS  Google Scholar 

  78. Mariat, D. et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age.BMC Microbiol.9, 123 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  79. Nordling, C. O. A new theory on cancer-inducing mechanism.Br. J. Cancer7, 68–72 (1953).

    Article CAS PubMed PubMed Central  Google Scholar 

  80. Vanhoutvin, S. A. et al. Butyrate-induced transcriptional changes in human colonic mucosa.PLoS ONE4, e6759 (2009).

    Article PubMed PubMed Central CAS  Google Scholar 

  81. Hamilton, W. D. The moulding of senescence by natural selection.J. Theor. Biol.12, 12–45 (1966).A pioneering paper that describes how several key factors (fertility, mortality and age) affect population dynamics.

    Article CAS PubMed  Google Scholar 

  82. Perry, S. et al. Infection withHelicobacter pylori is associated with protection against tuberculosis.PLoS ONE5, e8804 (2010).

    Article PubMed PubMed Central CAS  Google Scholar 

  83. Higgins, P. D. et al. PriorHelicobacter pylori infection amelioratesSalmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine.Inflamm. Bowel Dis.17, 1398–1408 (2011).

    Article PubMed  Google Scholar 

  84. Arnold, I. C. et al.Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells.J. Clin. Invest.121, 3088–3093 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  85. Atherton, J. C. & Blaser, M. J. Coadaptation ofHelicobacter pylori and humans: ancient history, modern implications.J. Clin. Invest.119, 2475–2487 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  86. Blaser, M. J. & Webb, G. Host demise as a beneficial function of indigenous microbiota in multicellular hosts. inAm. Soc. Microbiol. Conf. Beneficial Microbes (Lake Tahoe, Nevada, USA, 2005).

    Google Scholar 

  87. Patel, R. V. & Lebwohl, M. Psoriasis.Ann. Intern. Med.155, ITC2-1 (2011).

    Article  Google Scholar 

  88. Gao, Z., Tseng, C. H., Strober, B. E., Pei, Z. & Blaser, M. J. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions.PLoS ONE3, e2719 (2008).

    Article PubMed PubMed Central CAS  Google Scholar 

  89. Grice, E. A. & Segre, J. A. The skin microbiome.Nature Rev. Microbiol.9, 244–253 (2011).A comprehensive review of the skin microbiome and its connection to several diseases.

    Article CAS  Google Scholar 

  90. McDowell, A. et al. A novel multilocus sequence typing scheme for the opportunistic pathogenPropionibacterium acnes and characterization of type I cell surface-associated antigens.Microbiology157, 1990–2003 (2011).

    Article CAS PubMed  Google Scholar 

  91. Price, L. B. et al. Community analysis of chronic wound bacteria using 16S rRNA gene-based pyrosequencing: impact of diabetes and antibiotics on chronic wound microbiota.PLoS ONE4, e6462 (2009).

    Article PubMed PubMed Central CAS  Google Scholar 

  92. Grice, E. A. et al. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response.Proc. Natl Acad. Sci. USA107, 14799–1804 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  93. Andersson, A. F. et al. Comparative analysis of human gut microbiota by barcoded pyrosequencing.PLoS ONE3, e2836 (2008).

    Article PubMed PubMed Central CAS  Google Scholar 

  94. McColl, K. E.Helicobacter pylori infection.N. Engl. J. Med.362, 1597–1604 (2010).

    Article CAS PubMed  Google Scholar 

  95. el-Serag, H. B. & Sonnenberg, A. Opposing time trends of peptic ulcer and reflux disease.Gut43, 327–333 (1998).

    Article CAS PubMed PubMed Central  Google Scholar 

  96. Chen, Y. & Blaser, M. J. Inverse associations ofHelicobacter pylori with asthma and allergy.Arch. Intern. Med.167, 821–827 (2007).

    Article PubMed  Google Scholar 

  97. Plottel, C. S. & Blaser, M. J. Microbiome and malignancy.Cell Host Microbe10, 324–335 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  98. Lazarova, D. L., Bordonaro, M., Carbone, R. & Sartorelli, A. C. Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrate.Int. J. Cancer110, 523–531 (2004).

    Article CAS PubMed  Google Scholar 

  99. Wu, S. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses.Nature Med.15, 1016–1022 (2009).

    Article CAS PubMed  Google Scholar 

  100. Reikvam, D. H. et al. Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression.PLoS ONE6, e17996 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  101. Castellarin, M. et al.Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.Genome Res.22, 299–306 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  102. Kostic, A. D. et al. Genomic analysis identifies association ofFusobacterium with colorectal carcinoma.Genome Res.22, 292–298 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  103. Krisanaprakornkit, S. et al. Inducible expression of human β-defensin 2 byFusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier.Infect. Immun.68, 2907–2915 (2000).

    Article CAS PubMed PubMed Central  Google Scholar 

  104. Littman, D. R. & Pamer, E. G. Role of the commensal microbiota in normal and pathogenic host immune responses.Cell Host Microbe10, 311–323 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  105. Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine.Cell Host Microbe4, 337–349 (2008).An important study that describes the immunological interplay between segmented filamentous bacteria and Th17 cells in the distal small bowel.

    Article CAS PubMed PubMed Central  Google Scholar 

  106. Round, J. L. & Mazmanian, S. K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota.Proc. Natl Acad. Sci. USA107, 12204–12209 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  107. Ogura, Y. et al. A frameshift mutation inNOD2 associated with susceptibility to Crohn's disease.Nature411, 603–606 (2001).

    Article CAS PubMed  Google Scholar 

  108. Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.Nature411, 599–603 (2001).

    Article CAS PubMed  Google Scholar 

  109. Franchimont, D. et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis.Gut53, 987–992 (2004).

    Article CAS PubMed PubMed Central  Google Scholar 

  110. Ewaschuk, J. B., Tejpar, Q. Z., Soo, I., Madsen, K. & Fedorak, R. N. The role of antibiotic and probiotic therapies in current and future management of inflammatory bowel disease.Curr. Gastroenterol. Rep.8, 486–498 (2006).

    Article PubMed  Google Scholar 

  111. Hviid, A., Svanstrom, H. & Frisch, M. Antibiotic use and inflammatory bowel diseases in childhood.Gut60, 49–54 (2011).

    Article PubMed  Google Scholar 

  112. Manichanh, C. et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach.Gut55, 205–211 (2006).

    Article CAS PubMed PubMed Central  Google Scholar 

  113. Garrett, W. S. et al.Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis.Cell Host Microbe8, 292–300 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  114. Lepage, P. et al. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis.Gastroenterology141, 227–236 (2011).

    Article PubMed  Google Scholar 

  115. Mondot, S. et al. Highlighting new phylogenetic specificities of Crohn's disease microbiota.Inflamm. Bowel Dis.17, 185–192 (2011).

    Article CAS PubMed  Google Scholar 

  116. Abu-Shanab, A. & Quigley, E. M. The role of the gut microbiota in nonalcoholic fatty liver disease.Nature Rev. Gastroenterol. Hepatol.7, 691–701 (2010).

    Article  Google Scholar 

  117. Backhed, F., Manchester, J. K., Semenkovich, C. F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.Proc. Natl Acad. Sci. USA104, 979–984 (2007).

    Article CAS PubMed PubMed Central  Google Scholar 

  118. Mutlu, E. et al. Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats.Alcohol. Clin. Exp. Res.33, 1836–1846 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  119. Yan, A. W. et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease.Hepatology53, 96–105 (2011).

    Article CAS PubMed  Google Scholar 

  120. Fox, J. G. et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens.Gut59, 88–97 (2010).

    Article CAS PubMed  Google Scholar 

  121. Chen, Y. et al. Characterization of fecal microbial communities in patients with liver cirrhosis.Hepatology54, 562–572 (2011).

    Article PubMed  Google Scholar 

  122. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity.Nature444, 1022–1023 (2006).

    Article CAS PubMed  Google Scholar 

  123. Ajslev, T. A., Andersen, C. S., Gamborg, M., Sorensen, T. I. & Jess, T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics.Int. J. Obes.35, 522–529 (2011).

    Article CAS  Google Scholar 

  124. Luoto, R., Kalliomaki, M., Laitinen, K. & Isolauri, E. The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years.Int. J. Obes.34, 1531–1537 (2010).

    Article CAS  Google Scholar 

  125. Li, J. V. et al. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk.Gut60, 1214–1223 (2011).

    Article CAS PubMed  Google Scholar 

  126. Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria.Cell139, 485–498 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  127. Scher, J. U. & Abramson, S. B. The microbiome and rheumatoid arthritis.Nature Rev. Rheumatol.7, 569–578 (2011).

    Article CAS  Google Scholar 

  128. Hill, A. B. The environment and disease: association or causation?Proc. R. Soc. Med.58, 295–300 (1965).

    CAS PubMed PubMed Central  Google Scholar 

  129. Hentschel, E. et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication ofHelicobacter pylori and the recurrence of duodenal ulcer.N. Engl. J. Med.328, 308–312 (1993).

    Article CAS PubMed  Google Scholar 

  130. Devoy, A., Bunton-Stasyshyn, R. K., Tybulewicz, V. L., Smith, A. J. & Fisher, E. M. Genomically humanized mice: technologies and promises.Nature Rev. Genet.13, 14–20 (2012).

    Article CAS  Google Scholar 

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

    Article CAS PubMed  Google Scholar 

  132. Reshef, D. N. et al. Detecting novel associations in large data sets.Science334, 1518–1524 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  133. Islami, F. & Kamangar, F.Helicobacter pylori and esophageal cancer risk: a meta-analysis.Cancer Prev. Res.1, 329–338 (2008).

    Article CAS  Google Scholar 

  134. Blaser, M. J., Chen, Y. & Reibman, J. DoesHelicobacter pylori protect against asthma and allergy?Gut57, 561–567 (2008).

    Article PubMed  Google Scholar 

  135. Tana, C. et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome.Neurogastroenterol. Motil.22, 512–519 (2010).

    CAS PubMed  Google Scholar 

  136. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.Nature472, 57–63 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  137. Larsson, E. et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88.Gut 23 Nov 2011 (doi:10.1136/gutjnl-2011-301104).

  138. Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage.Proc. Natl Acad. Sci. USA101, 15718–15723 (2004).

    Article PubMed CAS PubMed Central  Google Scholar 

  139. Turnbaugh, P. J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.Sci. Transl. Med.1, 6ra14 (2009).

    Article PubMed PubMed Central CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH grants R01GM63270, R01DK090989, UH2 AR057506, 5 P30 CA016087 and 1UL1RR029893, the Diane Belfer Program for Human Microecology, the Michael Saperstein Medical Scholars Fund and the Levin Fellowship in Gastroenterology.

Author information

Authors and Affiliations

  1. Department of Medicine, NYU Langone Medical Center, New York, 10016, New York, USA

    Ilseung Cho & Martin J. Blaser

  2. New York Harbor Department of Veterans Affairs Medical Center (Manhattan), New York, 10010, New York, USA

    Ilseung Cho & Martin J. Blaser

  3. Department of Microbiology, NYU Langone Medical Center, New York, 10016, New York, USA

    Martin J. Blaser

  4. Department of Biology, New York University, New York, 10003, New York, USA

    Martin J. Blaser

Authors
  1. Ilseung Cho

    You can also search for this author inPubMed Google Scholar

  2. Martin J. Blaser

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toIlseung Cho.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Glossary

Microbiota

The microbial organisms that constitute the microbiome. The composition of the microbiota in a community can vary substantially between environmental sites, among host niches and between health and disease.

16S ribosomal RNA

A component of the 30S small subunit of prokaryotic ribosomes. Sequencing of the 16S rRNA has been used to identify prokaryotic taxonomy in complete environmental samples such as the microbiome.

Microbiome

The totality of microbes, their genetic information and the milieu in which they interact. Microbiomes typically consist of environmental or biological niches containing complex communities of microbes.

Metagenome

The genetic information of a complex population — typically from microbes in an environmental or host niche sample — that is constituted by the genomes of many individual organisms. The metagenome provides information about the functional genetic potential of the aggregate population.

Extinction

The loss of an organism or group of organisms (usually of a species) from an ecosystem.

Enterotype

A recently proposed classification unit of animals that is based on the bacteriological composition of their gut microbiome. There are reported to be at least three distinct enterotypes, which are independent of ethnic background and diet.

Nash equilibria

Concepts from game theory in which players know the strategies of the others, and in which any change from their strategy puts them in a less favourable position.

Resilience

A term in ecology indicating the capacity of a system to absorb disturbance and to reorganize itself while undergoing change, so as to retain essentially the same function, structure and identity.

Extirpations

The loss of species in a locality (for example, an individual host).

Allelopathy

A phenomenon in which a microbe uses chemical means to aid its competition within a group of microbes. Allelopathy may involve manipulation of third parties (for example, the host) to favour competition.

Mating preference

The selection or choice of sexual partners that is often based on traits of a potential mate. Genetic differences between selected and non-selected hosts are a source of selectable variation.

Antecubital fossae

The triangular areas on the anterior (flexor) aspects of elbow joints.

Popliteal fossae

The shallow depressions that are found on the flexor aspects of knee joints.

Pilosebaceous units

The anatomic structure around each hair shaft that consists of the hair shaft and follicle, the sebaceous gland and the erector pili muscle.

Amphibiont

An organism (for example, a microbe) that may have a pathogenic or symbiotic relationship with another organism (for example, its host), depending on context. This is a more specific term than commensal.

Lamina propria

A thin layer of loose connective tissue that lies underneath the epithelium; collectively these tissues constitute the mucosa that line various lumens in the body. The lamina propria is densely populated by immunological and inflammatory cells.

Steatosis

The pathological accumulation and retention of lipids in liver parenchymal cells. Substantial steatosis can compromise cellular functions and is associated with disease processes, including alcoholism, diabetes and hyperlipidaemia.

Commensals

Organisms (for example, microbes) that are involved in a form of symbiosis in which one organism derives a benefit while the other is unaffected.

Probiotic

Living microorganisms that are thought to confer a benefit to the host.

Roux-en-Y surgery

A type of gastric bypass surgery that is primarily used for the treatment of morbid obesity. In Roux-en-Y surgeries, a portion of the small bowel is bypassed to decrease the absorption of nutrients.

Dysbiosis

A condition in which the normal microbiome population structure is disturbed, often through external pressures such as disease states or medications.

Gnotobiotic

Describes an animal that is colonized solely by known strains of bacteria or other microorganisms. The term also describes germ-free animals, as the status of their microbial communities is known.

Conventionalization

A method in which germ-free animals (particularly mice) are inoculated with gut microbiota to populate the gastrointestinal tract.

Prebiotics

Food ingredients that confer specific changes in the gut microbiome and lead to beneficial effects in the host.

Operational taxonomic unit

(OTU). The smallest phylogenetic unit described by variations in 16S ribosomal RNA sequencing. Dissimilarity of <1% in 16S rRNA sequences has commonly been used to define an OTU but <3% and <5% have also been used.

Non-coexistence

An exclusivity scenario in which the abundance of one species leads to another species being less abundant than would be expected by chance.

Rights and permissions

About this article

Access through your institution
Buy or subscribe

Associated content

Collection

20th Anniversary

Series

Applications of next-generation sequencing

Advertisement

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for theNature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly.Sign up for Nature Briefing: Cancer

[8]ページ先頭

©2009-2025 Movatter.jp