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:

The human skin microbiome

Nature Reviews Microbiology volume 16, pages 143–155 (2018)Cite this article

Subjects

Key Points

  • Skin microorganisms have adapted to utilize the sparse nutrients available on the skin

  • Many cutaneous microorganisms can produce molecules that inhibit the colonization of other microorganisms or alter their behaviour

  • The skin microbiota of a healthy adult remains stable over time, despite environmental perturbations

  • Shotgun metagenomics provides greater resolution than traditional amplicon sequencing, enabling surveys of the skin microbiota at the kingdom, species, strain or gene level

  • Skin microorganisms have important roles in educating the innate and adaptive arms of the cutaneous immune system

  • Some skin diseases are associated with an altered microbial state; reversion of this dysbiosis may help prevent and/or treat the disease

Abstract

Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.

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: Amplicon versus shotgun metagenomic sequencing.
Figure 2: Skin microbial communities are shaped by physiological characteristics and the individual.
Figure 3: Skin commensal interactions with Staphylococcus aureus.
Figure 4: Formulating testable hypotheses from sequencing data to generate novel therapeutics.

Similar content being viewed by others

References

  1. Scharschmidt, T. C. & Fischbach, M. A. What lives on our skin: ecology, genomics and therapeutic opportunities of the skin microbiome. Drug Discov. Today Dis. Mech. 10, e83–e89 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Belkaid, Y. & Segre, J. A. Dialogue between skin microbiota and immunity. Science 346, 954–959 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Grice, E. A. The intersection of microbiome and host at the skin interface: genomic- and metagenomic-based insights. Genome Res. 25, 1514–1520 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kong, H. H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012). This is the first study in which the skin of individuals with atopic dermatitis was longitudinally sampled and sequenced.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Paulino, L. C., Tseng, C. H., Strober, B. E. & Blaser, M. J. Molecular analysis of fungal microbiota in samples from healthy human skin and psoriatic lesions. J. Clin. Microbiol. 44, 2933–2941 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kong, H. H. & Segre, J. A. Skin microbiome: looking back to move forward. J. Invest. Dermatol. 132, 933–939 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Woese, C. R. & Fox, G. E. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc. Natl Acad. Sci. USA 74, 5088–5090 (1977). This is the first study that used the 16S rRNA gene to infer the phylogeny of a microorganism.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schoch, C. L. et al. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc. Natl Acad. Sci. USA 109, 6241–6246 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Meisel, J. S. et al. Skin microbiome surveys are strongly influenced by experimental design. J. Invest. Dermatol. 136, 947–956 (2016). This paper describes how skin microbiome studies can be affected by methodology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zeeuwen, P. L. et al. Reply to Meisel et al. J. Investigative Dermatol. 137, 961–962 (2017).

    Article  CAS  Google Scholar 

  11. Castelino, M. et al. Optimisation of methods for bacterial skin microbiome investigation: primer selection and comparison of the 454 versus MiSeq platform. BMC Microbiol. 17, 23 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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 

  13. 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 

  14. Brooks, J. P. et al. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiol. 15, 66 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Yuan, S., Cohen, D. B., Ravel, J., Abdo, Z. & Forney, L. J. Evaluation of methods for the extraction and purification of DNA from the human microbiome. PLoS ONE 7, e33865 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gerasimidis, K. et al. The effect of DNA extraction methodology on gut microbiota research applications. BMC Res. Notes 9, 365 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Conlan, S. et al. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biol. 13, R64 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tomida, S. et al. Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. mBio 4, e000030-13 (2013).

    Article  CAS  Google Scholar 

  19. Bosi, E. et al. Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity. Proc. Natl Acad. Sci. USA 113, E3801–E3809 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Grice, E. A. & Segre, J. A. The skin microbiome. Nat. Rev. Microbiol. 9, 244–253 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Oh, J. et al. Biogeography and individuality shape function in the human skin metagenome. Nature 514, 59–64 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Findley, K. et al. Topographic diversity of fungal and bacterial communities in human skin. Nature 498, 367–370 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Oh, J. et al. Temporal stability of the human skin microbiome. Cell 165, 854–866 (2016). Together with reference 23, these studies explore the healthy human skin microbiome with shotgun metagenomic sequencing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hannigan, G. D. et al. The human skin double-stranded dna virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome. mBio 6, e01578-15 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Feng, H., Shuda, M., Chang, Y. & Moore, P. S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319, 1096–1100 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schloissnig, S. et al. Genomic variation landscape of the human gut microbiome. Nature 493, 45–50 (2013).

    Article  CAS  PubMed  Google Scholar 

  29. Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, 1237439 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tsai, Y. C. et al. Resolving the complexity of human skin metagenomes using single-molecule sequencing. mBio 7, e01948-15 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Holland, K. T., Greenman, J. & Cunliffe, W. J. Growth of cutaneous propionibacteria on synthetic medium; growth yields and exoenzyme production. J. Appl. Bacteriol. 47, 383–394 (1979).

    Article  CAS  PubMed  Google Scholar 

  32. Bruggemann, H. et al. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science 305, 671–673 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Marples, R. R., Downing, D. T. & Kligman, A. M. Control of free fatty acids in human surface lipids by Corynebacterium acnes. J. Invest. Dermatol. 56, 127–131 (1971).

    Article  CAS  PubMed  Google Scholar 

  34. Ingham, E., Holland, K. T., Gowland, G. & Cunliffe, W. J. Partial purification and characterization of lipase (EC 3.1.1.3) from Propionibacterium acnes. J. General Microbiol. 124, 393–401 (1981).

    CAS  Google Scholar 

  35. Gribbon, E. M., Cunliffe, W. J. & Holland, K. T. Interaction of Propionibacterium acnes with skin lipids in vitro. J. General Microbiol. 139, 1745–1751 (1993).

    Article  CAS  Google Scholar 

  36. Mukherjee, S. et al. Sebum and hydration levels in specific regions of human face significantly predict the nature and diversity of facial skin microbiome. Sci. Rep. 6, 36062 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Webster, G. F., Ruggieri, M. R. & McGinley, K. J. Correlation of Propionibacterium acnes populations with the presence of triglycerides on nonhuman skin. Appl. Environ. Microbiol. 41, 1269–1270 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wu, G. et al. Genus-wide comparative genomics of Malassezia delineates its phylogeny, physiology, and niche adaptation on human skin. PLoS Genet. 11, e1005614 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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. USA 107, 11971–11975 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mueller, N. T., Bakacs, E., Combellick, J., Grigoryan, Z. & Dominguez-Bello, M. G. The infant microbiome development: mom matters. Trends Mol. Med. 21, 109–117 (2015).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Faith, J. J., Colombel, J. F. & Gordon, J. I. Identifying strains that contribute to complex diseases through the study of microbial inheritance. Proc. Natl Acad. Sci. USA 112, 633–640 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Oh, J., Conlan, S., Polley, E. C., Segre, J. A. & Kong, H. H. Shifts in human skin and nares microbiota of healthy children and adults. Genome Med. 4, 77 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Jo, J. H. et al. Diverse human skin fungal communities in children converge in adulthood. J. Invest. Dermatol. 136, 2356–2363 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jo, J. H., Kennedy, E. A. & Kong, H. H. Topographical and physiological differences of the skin mycobiome in health and disease. Virulence 8, 324–333 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Havlickova, B., Czaika, V. A. & Friedrich, M. Epidemiological trends in skin mycoses worldwide. Mycoses 51 (Suppl. 4), 2–15 (2008).

    Article  PubMed  Google Scholar 

  47. Seebacher, C., Bouchara, J. P. & Mignon, B. Updates on the epidemiology of dermatophyte infections. Mycopathologia 166, 335–352 (2008).

    Article  PubMed  Google Scholar 

  48. Kyriakis, K. P. et al. Pityriasis versicolor prevalence by age and gender. Mycoses 49, 517–518 (2006).

    Article  PubMed  Google Scholar 

  49. von Eiff, C., Becker, K., Machka, K., Stammer, H. & Peters, G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med. 344, 11–16 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Weidenmaier, C., Goerke, C. & Wolz, C. Staphylococcus aureus determinants for nasal colonization. Trends Microbiol. 20, 243–250 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Bode, L. G. et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med. 362, 9–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. DeLeo, F. R., Otto, M., Kreiswirth, B. N. & Chambers, H. F. Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375, 1557–1568 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Proctor, R. A. Challenges for a universal Staphylococcus aureus vaccine. Clin. Infect. Dis. 54, 1179–1186 (2012).

    Article  CAS  PubMed  Google Scholar 

  54. Jansen, K. U., Girgenti, D. Q., Scully, I. L. & Anderson, A. S. Vaccine review: “Staphyloccocus aureus vaccines: problems and prospects”. Vaccine 31, 2723–2730 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Pamer, E. G. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science 352, 535–538 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ling, L. L. et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455–459 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Iwase, T. et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Sugimoto, S. et al. Staphylococcus epidermidis Esp degrades specific proteins associated with Staphylococcus aureus biofilm formation and host-pathogen interaction. J. Bacteriol. 195, 1645–1655 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zipperer, A. et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535, 511–516 (2016). Together with reference 57, these studies reveal how commensal skin microorganisms produce antimicrobials against S. aureus.

    Article  CAS  PubMed  Google Scholar 

  60. Nakatsuji, T. et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl Med. 9, eaah4680 (2017). This is the first study that used autologous transplant of microorganisms to the skin.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wollenberg, M. S. et al. Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation. mBio 5, e01286-14 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ramsey, M. M., Freire, M. O., Gabrilska, R. A., Rumbaugh, K. P. & Lemon, K. P. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium species. Front. Microbiol. 7, 1230 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Bomar, L., Brugger, S. D., Yost, B. H., Davies, S. S. & Lemon, K. P. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. mBio 7, e01725-15 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Christensen, G. J. et al. Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. BMC Genom. 17, 152 (2016).

    Article  CAS  Google Scholar 

  65. Janek, D., Zipperer, A., Kulik, A., Krismer, B. & Peschel, A. High frequency and diversity of antimicrobial activities produced by nasal Staphylococcus strains against bacterial competitors. PLoS Pathog. 12, e1005812 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Yassour, M. et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci. Transl Med. 8, 343ra81 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 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 

  68. Buffie, C. G. & Pamer, E. G. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13, 790–801 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Iebba, V. et al. Eubiosis and dysbiosis: the two sides of the microbiota. New Microbiol. 39, 1–12 (2016).

    CAS  PubMed  Google Scholar 

  70. Leyden, J. J., McGinley, K. J., Mills, O. H. & Kligman, A. M. Propionibacterium levels in patients with and without acne vulgaris. J. Invest. Dermatol. 65, 382–384 (1975).

    Article  CAS  PubMed  Google Scholar 

  71. Fitz-Gibbon, S. et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J. Invest. Dermatol. 133, 2152–2160 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kang, D., Shi, B., Erfe, M. C., Craft, N. & Li, H. Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis. Sci. Transl Med. 7, 293ra103 (2015). This is the first skin RNA sequencing study to compare microbial gene expression in individuals with and without acne.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Picardo, M., Ottaviani, M., Camera, E. & Mastrofrancesco, A. Sebaceous gland lipids. Dermatoendocrinol. 1, 68–71 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Jahns, A. C. et al. An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study. Br. J. Dermatol. 167, 50–58 (2012).

    Article  CAS  PubMed  Google Scholar 

  75. Lomholt, H. B. & Kilian, M. Population genetic analysis of Propionibacterium acnes identifies a subpopulation and epidemic clones associated with acne. PLoS ONE 5, e12277 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. McDowell, A. et al. An expanded multilocus sequence typing scheme for Propionibacterium acnes: investigation of 'pathogenic', 'commensal' and antibiotic resistant strains. PLoS ONE 7, e41480 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. McDowell, A., Nagy, I., Magyari, M., Barnard, E. & Patrick, S. The opportunistic pathogen Propionibacterium acnes: insights into typing, human disease, clonal diversification and CAMP factor evolution. PLoS ONE 8, e70897 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Omer, H., McDowell, A. & Alexeyev, O. A. Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies. Clin. Dermatol. 35, 118–129 (2017).

    Article  PubMed  Google Scholar 

  79. Balta, I. & Ozuguz, P. Vitamin B12-induced acneiform eruption. Cutane. Ocular Toxicol. 33, 94–95 (2014).

    Article  Google Scholar 

  80. Sherertz, E. F. Acneiform eruption due to “megadose” vitamins B6 and B12. Cutis 48, 119–120 (1991).

    CAS  PubMed  Google Scholar 

  81. Dupre, A., Albarel, N., Bonafe, J. L., Christol, B. & Lassere, J. Vitamin B-12 induced acnes. Cutis 24, 210–211 (1979).

    CAS  PubMed  Google Scholar 

  82. Braun-Falco, O. & Lincke, H. The problem of vitamin B6/B12 acne. A contribution on acne medicamentosa [German]. MMW Munch. Med. Wochenschr. 118, 155–160 (1976).

    CAS  PubMed  Google Scholar 

  83. Puissant, A., Vanbremeersch, F., Monfort, J. & Lamberton, J. N. A new iatrogenic dermatosis: acne caused by vitamin B 12 [French]. Bull. Soc. Fr. Dermatol. Syphiligr. 74, 813–815 (1967).

    CAS  PubMed  Google Scholar 

  84. Johnson, T., Kang, D., Barnard, E. & Li, H. Strain-level differences in porphyrin production and regulation in Propionibacterium acnes elucidate disease associations. mSphere 1, e00023-15 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Palmer, C. N. et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 38, 441–446 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. The EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat. Genet. 47, 1449–1456 (2015).

  87. Leyden, J. J., Marples, R. R. & Kligman, A. M. Staphylococcus aureus in the lesions of atopic dermatitis. Br. J. Dermatol. 90, 525–530 (1974).

    Article  CAS  PubMed  Google Scholar 

  88. Huang, J. T., Abrams, M., Tlougan, B., Rademaker, A. & Paller, A. S. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics 123, e808–814 (2009).

    Article  PubMed  Google Scholar 

  89. Bath-Hextall, F. J., Birnie, A. J., Ravenscroft, J. C. & Williams, H. C. Interventions to reduce Staphylococcus aureus in the management of atopic eczema: an updated Cochrane review. Br. J. Dermatol. 163, 12–26 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Byrd, A. L. et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci. Transl Med. 9, eaal4651 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kennedy, E. A. et al. Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J. Allergy Clin. Immunol. 139, 166–172 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Chng, K. R. et al. Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. Nat. Microbiol. 1, 16106 (2016).

    Article  CAS  PubMed  Google Scholar 

  93. Hanski, I. et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc. Natl Acad. Sci. USA 109, 8334–8339 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Fyhrquist, N. et al. Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation. J. Allergy Clin. Immunol. 134, 1301–1309.e11 (2014).

    Article  CAS  PubMed  Google Scholar 

  95. Zeeuwen, P. L. et al. Gram-positive anaerobe cocci are underrepresented in the microbiome of filaggrin-deficient human skin. J. Allergy Clin. Immunol. 139, 1368–1371 (2017).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Niebuhr, M. et al. Staphylococcal alpha-toxin is a strong inducer of interleukin-17 in humans. Infect. Immun. 79, 1615–1622 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kaesler, S. et al. Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2. J. Allergy Clin. Immunol. 138, 780–790.e6 (2016).

    Article  CAS  PubMed  Google Scholar 

  99. Zhang, L. J. et al. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 347, 67–71 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Nakatsuji, T. et al. Staphylococcus aureus exploits epidermal barrier defects in atopic dermatitis to trigger cytokine expression. J. Invest. Dermatol. 136, 2192–2200 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kobayashi, T. et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 42, 756–766 (2015). This study demonstrates how S. aureus predominance can drive skin inflammation in an animal model of altered barrier integrity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Oh, J. et al. The altered landscape of the human skin microbiome in patients with primary immunodeficiencies. Genome Res. 23, 2103–2114 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Smeekens, S. P. et al. Skin microbiome imbalance in patients with STAT1/STAT3 defects impairs innate host defense responses. J. Innate Immun. 6, 253–262 (2014).

    Article  CAS  PubMed  Google Scholar 

  104. Chu, E. Y. et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch. Dermatol. 148, 79–84 (2012).

    Article  CAS  PubMed  Google Scholar 

  105. Prompers, L. et al. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia 50, 18–25 (2007).

    Article  CAS  PubMed  Google Scholar 

  106. Valensi, P., Girod, I., Baron, F., Moreau-Defarges, T. & Guillon, P. Quality of life and clinical correlates in patients with diabetic foot ulcers. Diabetes Metab. 31, 263–271 (2005).

    Article  CAS  PubMed  Google Scholar 

  107. Ramsey, S. D. et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 22, 382–387 (1999).

    Article  CAS  PubMed  Google Scholar 

  108. Gardner, S. E., Hillis, S. L., Heilmann, K., Segre, J. A. & Grice, E. A. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes 62, 923–930 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Loesche, M. et al. Temporal stability in chronic wound microbiota is associated with poor healing. J. Invest. Dermatol. 137, 237–244 (2017).

    Article  CAS  PubMed  Google Scholar 

  110. Martinez, C. et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am. J. Gastroenterol. 103, 643–648 (2008).

    Article  PubMed  Google Scholar 

  111. Kalan, L. et al. Redefining the chronic-wound microbiome: fungal communities are prevalent, dynamic, and associated with delayed healing. mBio 7, e01058-16 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Korem, T. et al. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science 349, 1101–1106 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Segre, J. A. Epidermal barrier formation and recovery in skin disorders. J. Clin. Invest. 116, 1150–1158 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gallo, R. L. & Hooper, L. V. Epithelial antimicrobial defence of the skin and intestine. Nat. Rev. Immunol. 12, 503–516 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kong, H. H. et al. Performing skin microbiome research: a method to the madness. J. Invest. Dermatol. 137, 561–568 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Alexeyev, O. A. Bacterial landscape of human skin: seeing the forest for the trees. Exp. Dermatol. 22, 443–446 (2013).

    Article  CAS  PubMed  Google Scholar 

  117. Alexeyev, O. A. & Jahns, A. C. Sampling and detection of skin Propionibacterium acnes: current status. Anaerobe 18, 479–483 (2012).

    Article  CAS  PubMed  Google Scholar 

  118. Grice, E. A. et al. A diversity profile of the human skin microbiota. Genome Res. 18, 1043–1050 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Nakatsuji, T. et al. The microbiome extends to subepidermal compartments of normal skin. Nat. Commun. 4, 1431 (2013).

    Article  CAS  PubMed  Google Scholar 

  120. Zeeuwen, P. L. et al. Microbiome dynamics of human epidermis following skin barrier disruption. Genome Biol. 13, R101 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Nagy, I. et al. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect. 8, 2195–2205 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Naik, S. et al. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520, 104–108 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012). This study shows that skin commensals can promote cutaneous adaptive immunity to pathogens.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. PrabhuDas, M. et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat. Immunol. 12, 189–194 (2011).

    Article  CAS  PubMed  Google Scholar 

  125. Scharschmidt, T. C. et al. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 43, 1011–1021 (2015). This study describes how FoxP3+ T cells accumulate in neonatal skin and promote tolerance to commensals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Belkaid, Y. & Tamoutounour, S. The influence of skin microorganisms on cutaneous immunity. Nat. Rev. Immunol. 16, 353–366 (2016). This is a notable Review on the roles of different microorganisms in educating innate and adaptive components of the skin immune system.

    Article  CAS  PubMed  Google Scholar 

  127. Belkaid, Y. & Harrison, O. J. Homeostatic immunity and the microbiota. Immunity 46, 562–576 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. 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 

  129. Otto, M. Staphylococcus epidermidis — the 'accidental' pathogen. Nat. Rev. Microbiol. 7, 555–567 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Newell, E. W. & Davis, M. M. Beyond model antigens: high-dimensional methods for the analysis of antigen-specific T cells. Nat. Biotechnol. 32, 149–157 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Division of Intramural Research of the National Human Genome Research Institute and the National Institute of Allergy and Infectious Diseases.

Author information

Authors and Affiliations

  1. Microbial Genomics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Allyson L. Byrd & Julia A. Segre

  2. Department of Bioinformatics, Boston University, Boston, 02215, Massachusetts, USA

    Allyson L. Byrd

  3. Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Allyson L. Byrd & Yasmine Belkaid

  4. Department of Cancer Immunology, Genentech, South San Francisco, 94080, California, USA

    Allyson L. Byrd

  5. Department of Intramural Research, National Institute of Allergy and Infectious Diseases Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Yasmine Belkaid

Authors
  1. Allyson L. Byrd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasmine Belkaid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia A. Segre
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.L.B., Y.B. and J.A.S. contributed to researching data for article. A.L.B., Y.B. and J.A.S. substantially contributed to the discussion of content. A.L.B. and J.A.S. wrote the article. A.L.B., Y.B. and J.A.S. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Julia A. Segre.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Microbiota

An aggregate of microorganisms, including bacteria, archaea, protists, fungi and viruses.

Microbiome

The composition of all microbial genes in a community.

Amplicons

Segments of DNA or RNA that are targeted with primers and amplified in PCR.

Amplicon sequencing

Querying microbial constituents of a community by targeted amplification and sequencing of a conserved marker gene.

Reference genomes

Sequenced and assembled genomic content of a species with genes oriented as they appear on the chromosome.

Shotgun metagenomics sequencing

Unrestricted sequencing of all genomic material present in a clinical or an environmental sample.

Virome

The composition of all viral genes in a community.

Colonization resistance

A mechanism where commensal microorganisms prevent the colonization of harmful microorganisms.

Prebiotic

A substance, such as carbohydrate or fibre, that promotes the growth of beneficial bacteria.

Probiotic

Live microorganisms that are administered or consumed to confer a health benefit on the host.

Sebum

A mixture of lipids produced by sebaceous glands to lubricate and protect the skin.

Stratum corneum

The outermost layer of the epidermis composed of dead, mature skin cell keratinocytes.

Anoxic

A lack or absence of oxygen.

Sebaceous gland

An exocrine gland in the skin, usually attached to hair follicles, that secretes sebum.

Auxotrophic

An organism that is unable to synthesize a particular compound required for its growth.

Mycobiome

The composition of all fungal genes in a community.

Bacteriocin

An antimicrobial peptide produced by bacteria to inhibit or kill closely related or non-related bacteria.

Dysbiosis

A microbial community that is altered or impaired compared with normal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nat Rev Microbiol 16, 143–155 (2018). https://doi.org/10.1038/nrmicro.2017.157

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro.2017.157

This article is cited by

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