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.

  • Review Article
  • Published:

Microbiota—implications for immunity and transplantation

Key Points

  • Measuring the microbiome and/or microbiota is challenging; new bioinformatic techniques are becoming available that can help identify patterns in complex data sets

  • Numerous pre-clinical studies show that the microbiota has profound effects on the host immune system, which can influence the balance between tolerance and immunity

  • Microbial species and gene catalogues can help identify diagnostic biomarkers that correlate with outcomes in organ transplant recipients

  • Functional analyses of the microbiota will be required to characterize specific pathophysiological pathways and define therapeutic interventions

  • Clinical studies will be required to correlate features of the microbiota with the outcomes of organ transplantation, including graft survival, infection, rejection, recurrent disease, inflammation, alloreactivity and fibrosis

  • Challenges lie in translating associations between the microbiota and transplantation outcomes into definitive demonstrations of mechanism and causality, which are limitations that currently plague clinical investigation of the microbiota

Abstract

Each individual harbours a unique set of commensal microorganisms, collectively referred to as the microbiota. Notably, these microorganisms exceed the number of cells in the human body by 10-fold. This finding has accelerated a shift in our understanding of human physiology, with the realization that traits necessary for health are both encoded and influenced by the human genome and the microbiota. Our understanding of the aetiology of complex diseases has, therefore, evolved with increasing awareness that the human microbiota has an active and critical role in maintaining health and inducing disease. Indeed, findings from bioinformatic studies indicate that the microbiota and microbiome have multiple effects on the innate and adaptive immune systems, with effects on infection, autoimmune disease and cancer. In this Review, we first address the important statistical and informatics aspects that should be considered when characterizing the composition of microbiota. We next highlight the effects of the microbiota on the immune system and the implications of these effects on organ failure and transplantation. Finally, we reflect on the future perspectives for studies of the microbiota, including novel diagnostic tests and therapeutics.

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

Access options

Buy this article

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

Figure 1: Overview of the processing and analysis steps of 16S rRNA gene sequencing data (Illumina MiSeq® [San Diego, USA] paired-reads).
Figure 2: Interaction between the microbiota and immune system at the mucosal surface.
Figure 3: The relationship between microbiota and alloimmunity.
Figure 4: Translating microbiota and clinical data to therapeutic strategies.

Similar content being viewed by others

References

  1. Savage, D. C. Microbial Ecology of the Gastrointestinal Tract. Annu. Rev. Microbiol. 31, 107–133 (1977).

    Article  CAS  PubMed  Google Scholar 

  2. National Research Council (US) Committee on Metagenomics: Challenges and Functional Applications. The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet. (National Academies Press [US], 2007).

  3. Kostic, A. D., Xavier, R. J. & Gevers, D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146, 1489–1499 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Weng, M. & Walker, W. A. The role of gut microbiota in programming the immune phenotype. J. Dev. Orig. Health Dis. 4, 203–214 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Schwabe, R. F. & Jobin, C. The microbiome and cancer. Nat. Rev. Cancer 13, 800–812 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stecher, B. & Hardt, W.-D. The role of microbiota in infectious disease. Trends Microbiol. 16, 107–114 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Wu, H.-J. & Wu, E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3, 4–14 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fricke, W. F., Maddox, C., Song, Y. & Bromberg, J. S. Human microbiota characterization in the course of renal transplantation. Am. J. Transplant. 14, 416–427 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Oh, P. L. et al. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am. J. Transplant. 12, 753–762 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Jenq, R. R. et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J. Exp. Med. 209, 903–911 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. National Institutes of Health. Human microbiome project [online], (2015).

  12. MetaHIT. Metagenomics of the human intestinal tract [online], (2012).

  13. Weisburg, W. G., Barns, S. M., Pelletier, D. A. & Lane, D. J. 16S ribosomal DNA amplification for phylogenetic study. J. Bacteriol. 173, 697–703 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Handelsman, J., Rondon, M. R., Brady, S. F., Clardy, J. & Goodman, R. M. Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem. Biol. 5, R245–249 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Langille, M. G. I. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814–821 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. RDP release 11. Sequence analysis tools [online], (2014).

  17. Silva. High quality ribosomal RNA databases [online], (2014).

  18. Green genes. 16S rDNA data and tools [online], (2013).

  19. DeSantis, T. Z. et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72, 5069–5072 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schloss, P. D. & Handelsman, J. Introducing DOTUR, a computer program for defining operational taxonomic units and estimating species richness. Appl. Environ. Microbiol. 71, 1501–1506 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hill, T. C. J., Walsh, K. A., Harris, J. A. & Moffett, B. F. Using ecological diversity measures with bacterial communities. FEMS Microbiol. Ecol. 43, 1–11 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schloss, P. D. et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75, 7537–7541 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lozupone, C. A., Hamady, M., Kelley, S. T. & Knight, R. Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities. Appl. Environ. Microbiol. 73, 1576–1585 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Magurran, A. E. Measuring Biological Diversity (Wiley-Blackwell, 2004).

    Google Scholar 

  26. Lozupone, C. & Knight, R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl. Environ. Microbiol. 71, 8228–8235 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Romero, R. et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome 2, 4 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  28. McGarigal, K., Landguth, E. & Stafford, S. Multivariate Statistics for Wildlife and Ecology Research (Springer, 2002).

    Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xia, L. C. et al. Extended local similarity analysis (eLSA) of microbial community and other time series data with replicates. BMC Syst. Biol. 5 (Suppl. 2), S15 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Segata, N. et al. Metagenomic biomarker discovery and explanation. Genome Biol. 12, R60 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Matsumoto, S., Setoyama, H. & Umesaki, Y. Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization. Gastroenterology 103, 1777–1782 (1992).

    Article  CAS  PubMed  Google Scholar 

  33. Lundin, A. et al. Gut flora, Toll-like receptors and nuclear receptors: a tripartite communication that tunes innate immunity in large intestine. Cell. Microbiol. 10, 1093–1103 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Campos Canesso, M. et al. Comparing the effects of acute alcohol consumption in germ-free and conventional mice: the role of the gut microbiota. BMC Microbiol. 14, 240 (2014).

    Article  CAS  Google Scholar 

  35. Seki, E. et al. TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat. Med. 13, 1324–1332 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Turley, S. J., Lee, J. W., Dutton-Swain, N., Mathis, D. & Benoist, C. Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc. Natl Acad. Sci. USA 102, 17729–17733 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl Acad. Sci. USA 106, 3698–3703 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hänninen, A. et al. Islet beta-cell-specific T cells can use different homing mechanisms to infiltrate and destroy pancreatic islets. Am. J. Pathol. 170, 240–250 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Molloy, M., Bouladoux, N. & Belkaid, Y. Intestinal Microbiota: Shaping local and systemic immune responses. Semin. Immunol. 24, 58–66 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).

    Article  CAS  PubMed  Google Scholar 

  41. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Glaister, J. R. Factors affecting the lymphoid cells in the small intestinal epithelium of the mouse. Int. Arch. Allergy Immunol. 45, 719–730 (1973).

    Article  CAS  Google Scholar 

  44. Pollard, M. & Sharon, N. Responses of the peyer's patches in germ-free mice to antigenic stimulation. Infect. Immun. 2, 96–100 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hoshi, H. et al. Lymph follicles and germinal centers in popliteal lymph nodes and other lymphoid tissues of germ-free and conventional rats. Tohoku J. Exp. Med. 166, 297–307 (1992).

    Article  CAS  PubMed  Google Scholar 

  46. Clarke, T. B. et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16, 228–231 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rivas, M. N. et al. MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice. J. Clin. Invest. 122, 1933–1947 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sakaguchi, S. et al. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol. Rev. 212, 8–27 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Chinen, T., Volchkov, P. Y., Chervonsky, A. V. & Rudensky, A. Y. A critical role for regulatory T cell-mediated control of inflammation in the absence of commensal microbiota. J. Exp. Med. 207, 2323–2330 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bang, C., Weidenbach, K., Gutsmann, T., Heine, H. & Schmitz, R. A. The intestinal archaea Methanosphaera stadtmanae and Methanobrevibacter smithii activate human dendritic cells. PLoS ONE 9, e99411 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Stepankova, R. et al. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm. Bowel Dis. 13, 1202–1211 (2007).

    Article  PubMed  Google Scholar 

  53. Niess, J. H., Leithäuser, F., Adler, G. & Reimann, J. Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. J. Immunol. 180, 559–568 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Bermudez-Brito, M. et al. Human intestinal dendritic cells decrease cytokine release against salmonella infection in the presence of Lactobacillus paracasei upon TLR activation. PLoS ONE 7, e43197 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.0804812105.

  56. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    Article  CAS  PubMed  Google Scholar 

  58. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. 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  PubMed  PubMed Central  Google Scholar 

  60. Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013).

    Article  CAS  PubMed  Google Scholar 

  61. Dewhirst, F. E. et al. Phylogeny of the defined murine microbiota: altered Schaedler flora. Appl. Environ. Microbiol. 65, 3287–3292 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Geuking, M. B. et al. Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34, 794–806 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Josefowicz, S. Z. et al. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482, 395–399 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lathrop, S. K. et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 478, 250–254 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chehoud, C. et al. Complement modulates the cutaneous microbiome and inflammatory milieu. Proc. Natl Acad. Sci. USA 110, 15061–15066 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Kurashima, Y. et al. The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. Immunity 40, 530–541 (2014).

    Article  CAS  PubMed  Google Scholar 

  67. Nakamura, Y. et al. Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature 503, 397–401 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Canesso, M. C. C. et al. Skin wound healing is accelerated and scarless in the absence of commensal microbiota. J. Immunol. 193, 5171–5180 (2014).

    Article  CAS  PubMed  Google Scholar 

  69. Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Shen, W. et al. Adaptive immunity to murine skin commensals. Proc. Natl Acad. Sci. USA 111, E2977–E2986 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lai, Y. et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat. Med. 15, 1377–1382 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fyhrquist, N. et al. Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation. J. Allergy Clin. Immunol. 136, 1301–1309 (2014).

    Article  CAS  Google Scholar 

  73. Volz, T. et al. Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells. J. Invest. Dermatol. 134, 96–104 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl Acad. Sci. USA 108, 5354–5359 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Gollwitzer, E. S. et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20, 642–647 (2014).

    Article  CAS  PubMed  Google Scholar 

  76. Nicolle, L. E. et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin. Infect. Dis. 40, 643–654 (2005).

    Article  PubMed  Google Scholar 

  77. Xu, W. et al. Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am. J. Clin. Exp. Urol. 2, 57–61 (2014).

    PubMed  PubMed Central  Google Scholar 

  78. Cheng, Y.-W. & Wong, S.-N. Diagnosing symptomatic urinary tract infections in infants by catheter urine culture. J. Paediatr. Child Health 41, 437–440 (2005).

    Article  PubMed  Google Scholar 

  79. Siddiqui, H., Nederbragt, A. J., Lagesen, K., Jeansson, S. L. & Jakobsen, K. S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 11, 244 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Siddiqui, H., Lagesen, K., Nederbragt, A. J., Jeansson, S. L. & Jakobsen, K. S. Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol. 12, 205 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Hilt, E. E. et al. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J. Clin. Microbiol. 52, 871–876 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Wen, L. et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455, 1109–1113 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Endesfelder, D. et al. Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes 63, 2006–2014 (2014).

    Article  CAS  PubMed  Google Scholar 

  84. Bauer, H., Horowitz, R. E., Levenson, S. M. & Popper, H. The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am. J. Pathol. 42, 471–483 (1963).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Koren, O. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc. Natl Acad. Sci. USA 108, 4592–4598 (2011).

    Article  PubMed  Google Scholar 

  87. Oh, J. Z. et al. TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination. Immunity 41, 478–492 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Andrade-Oliveira, V. et al. Gut bacteria products prevent AKI induced by ischemia-reperfusion. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014030288.

  89. Harkiolaki, M. et al. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity 30, 348–357 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Pantenburg, B., Heinzel, F., Das, L., Heeger, P. S. & Valujskikh, A. T cells primed by Leishmania major infection cross-react with alloantigens and alter the course of allograft rejection. J. Immunol. 169, 3686–3693 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Atkinson, M. A. et al. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J. Clin. Invest. 94, 2125–2129 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. McClain, M. T. et al. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat. Med. 11, 85–89 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Lunardi, C. et al. Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells. Nat. Med. 6, 1183–1186 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Holdener, M. et al. Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J. Exp. Med. 205, 1409–1422 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhao, Z.-S., Granucci, F., Yeh, L., Schaffer, P. A. & Cantor, H. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 279, 1344–1347 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Bachmaier, K. et al. Chlamydia infections and heart disease linked through antigenic mimicry. Science 283, 1335–1339 (1999).

    Article  CAS  PubMed  Google Scholar 

  97. Westall, F. C. Molecular mimicry revisited: gut bacteria and multiple sclerosis. J. Clin. Microbiol. 44, 2099–2104 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Amedei, A. et al. Molecular mimicry between Helicobacter pylori antigens and H+, K+—adenosine triphosphatase in human gastric autoimmunity. J. Exp. Med. 198, 1147–1156 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Deshmukh, U. S. et al. HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. J. Autoimmun. 37, 254–262 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kirvan, C. A., Swedo, S. E., Heuser, J. S. & Cunningham, M. W. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat. Med. 9, 914–920 (2003).

    Article  CAS  PubMed  Google Scholar 

  101. Massa, M. et al. Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis. Arthritis Rheum. 46, 3015–3025 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. Ciubotariu, R. et al. Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts. J. Clin. Invest. 101, 398–405 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Amir, A. L. et al. Allo-HLA reactivity of virus-specific memory T cells is common. Blood 115, 3146–3157 (2010).

    Article  CAS  PubMed  Google Scholar 

  104. Brehm, M. A. et al. Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity. Am. J. Transplant. 10, 1738–1748 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. D'Orsogna, L. J. A. et al. Vaccine-induced allo-HLA-reactive memory T cells in a kidney transplantation candidate. Transplantation 91, 645–651 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. Hudson, K. E., Lin, E., Hendrickson, J. E., Lukacher, A. E. & Zimring, J. C. Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope. Blood 115, 3989–3996 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Abt, M. C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158–170 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Maier, S. et al. Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28−/− mice. Nat. Med. 7, 557–562 (2001).

    Article  CAS  PubMed  Google Scholar 

  109. Morita, K. et al. Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and progression of acute allograft rejection. J. Immunol. 167, 2979–2984 (2001).

    Article  CAS  PubMed  Google Scholar 

  110. Tanaka, K., Sawamura, S., Satoh, T., Kobayashi, K. & Noda, S. Role of the indigenous microbiota in maintaining the virus-specific CD8 memory T cells in the lung of mice infected with murine cytomegalovirus. J. Immunol. 178, 5209–5216 (2007).

    Article  CAS  PubMed  Google Scholar 

  111. Schwab, L. et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat. Med. 20, 648–654 (2014).

    Article  CAS  PubMed  Google Scholar 

  112. Taur, Y. et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124, 1174–1182 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hall, J. A. et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29, 637–649 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Hand, T. W. et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337, 1553–1556 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Oldenhove, G. et al. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal Infection. Immunity 31, 772–786 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Vaziri, N. D. et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 83, 308–315 (2013).

    Article  PubMed  Google Scholar 

  117. Qin, N. et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 513, 59–64 (2014).

    Article  CAS  PubMed  Google Scholar 

  118. Diaz, P. I. et al. Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome. Clin. Vaccine Immunol. 20, 920–930 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Li, Q. R. et al. Reciprocal interaction between intestinal microbiota and mucosal lymphocyte in cynomolgus monkeys after alemtuzumab treatment. Am. J. Transplant. 13, 899–910 (2013).

    Article  CAS  PubMed  Google Scholar 

  120. Li, Q., Wang, C., Tang, C., He, Q. & Li, J. Lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal microbiota in cynomolgus monkeys. Transplantation 98, 951–959 (2014).

    Article  CAS  PubMed  Google Scholar 

  121. Soave, R. Prophylaxis strategies for solid-organ transplantation. Clin. Infect. Dis. 33 (Suppl. 1), S26–S31 (2001).

    Article  PubMed  Google Scholar 

  122. 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  CAS  PubMed  PubMed Central  Google Scholar 

  123. Antunes, L. C. M. et al. Effect of antibiotic treatment on the intestinal metabolome. Antimicrob. Agents Chemother. 55, 1494–1503 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  125. Modi, S. R., Lee, H. H., Spina, C. S. & Collins, J. J. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499, 219–222 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. 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, 4554–4561 (2011).

    Article  PubMed  Google Scholar 

  127. Bouatra, S. et al. The human urine metabolome. PLoS ONE 8, e73076 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Youngster, I. et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 312, 1772–1778 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Macdonald, W. A. et al. T cell allorecognition via molecular mimicry. Immunity 31, 897–908 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Jonathan S. Bromberg.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bromberg, J., Fricke, W., Brinkman, C. et al. Microbiota—implications for immunity and transplantation. Nat Rev Nephrol 11, 342–353 (2015). https://doi.org/10.1038/nrneph.2015.70

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2015.70

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

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