Review Article | Published:

The skin microbiome

Nature Reviews Microbiology volume 9, pages 244253 (2011) | Download Citation

  • A Corrigendum to this article was published on 27 June 2011

This article has been updated

Abstract

The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.

Key points

  • The skin is a physical barrier against invasion by pathogenic organisms and foreign substances. The skin is also an ecosystem, host to a microbial milieu that, for the most part, is harmless.

  • The habitat of the skin varies topographically and is likely to be associated with variation in the colonizing microbiota. Factors contributing to variation in the skin microbiota include the density of hair follicles and glands (sweat or sebaceous), host factors (such as age and sex) and environmental factors (such as occupation, climate and hygiene).

  • Analysing skin bacterial microbiota by sequencing of 16S ribosomal RNA genes reveals a greater diversity of organisms than has been found by culture-based methods.

  • The microenvironment of the skin site sampled determines to a large extent the colonization by the predominant species, the temporal variation and the interpersonal variation. Propionibacterium spp. predominate in sebaceous areas, Corynebacterium and Staphylococcus spp. predominate in moist areas, and dry areas exhibit the greatest amount of diversity.

  • Compared with other mucosal microbiomes, the skin microbiome shows the greatest variability over time and harbours the greatest phylogenetic diversity.

  • The cutaneous immune system modulates colonization by the microbiota and is also vital during infection and wounding. Dysregulation of the skin immune response is evident in several skin disorders.

  • A wide range of skin disorders are postulated to arise in part owing to a microbial component. These disorders include atopic dermatitis, acne, seborrhoeic dermatitis and chronic wounds. Additionally, commensal bacteria (for example, Staphylococcus epidermidis) can become pathogenic and cause invasive infection.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 27 June 2011

    It has been brought to our attention that in FIG. 1 of the original article the morphology and localization of the Demodex mites were not accurate. We have corrected the figure to show a cartoon that is more representative of the straight body and short limbs of these mites, and of their localization in the hair follicle. The correct figure is now shown. We thank I. Dekio for bringing this to our attention and apologize to readers for any confusion caused.

References

  1. 1.

    , & Skin microflora and bacterial infections of the skin. J. Investig. Dermatol. Symp. Proc. 6, 170–174 (2001).

  2. 2.

    Microbial ecology of human skin in health and disease. J. Investig. Dermatol. Symp. Proc. 6, 167–169 (2001).

  3. 3.

    The Ecology of the Human Skin (Charles C Thomas, Bannerstone House, Springfield, Illinois, 1965). A seminal and comprehensive work of classical dermatological microbiology.

  4. 4.

    & Microbial ecology of the skin. Annu. Rev. Microbiol. 42, 441–464 (1988).

  5. 5.

    Skin microbiology: coming of age. J. Med. Microbiol. 17, 1–12 (1984).

  6. 6.

    & Microbiology of the skin: resident flora, ecology, infection. J. Am. Acad. Dermatol. 20, 367–390 (1989).

  7. 7.

    , & Skin microbiota: a source of disease or defence? Br. J. Dermatol. 158, 442–455 (2008).

  8. 8.

    Location-related differences in structure and function of the stratum corneum with special emphasis on those of the facial skin. Int. J. Cosmet Sci. 30, 413–434 (2008).

  9. 9.

    , & The skin: an indispensable barrier. Exp. Dermatol. 17, 1063–1072 (2008).

  10. 10.

    The skin barrier as an innate immune element. Semin. Immunopathol. 29, 3–14 (2007).

  11. 11.

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

  12. 12.

    & Getting under the skin of epidermal morphogenesis. Nature Rev. Genet. 3, 199–209 (2002).

  13. 13.

    , & The microbial ecology of pilosebaceous units isolated from human skin. J. Gen. Microbiol. 130, 803–807 (1984).

  14. 14.

    In search of human skin pheromones. Arch. Dermatol. 130, 1048–1051 (1994).

  15. 15.

    & The sequential action of a dipeptidase and a β-lyase is required for the release of the human body odorant 3-methyl-3-sulfanylhexan-1-ol from a secreted Cys-Gly-(S) conjugate by Corynebacteria. J. Biol. Chem. 283, 20645–20652 (2008).

  16. 16.

    , , & Production of malodorous steroids from androsta-5,16-dienes and androsta-4,16-dienes by Corynebacteria and other human axillary bacteria. J. Steroid Biochem. Mol. Biol. 87, 327–336 (2003).

  17. 17.

    et al. A functional ABCC11 allele is essential in the biochemical formation of human axillary odor. J. Invest. Dermatol. 130, 529–540 (2010).

  18. 18.

    , , , & A specific bacterial aminoacylase cleaves odorant precursors secreted in the human axilla. J. Biol. Chem. 278, 5718–5727 (2003).

  19. 19.

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

  20. 20.

    , & Control of free fatty acids in human surface lipids by Corynebacterium acnes. J. Invest. Dermatol. 56, 127–131 (1971).

  21. 21.

    , , & Partial purification and characterization of lipase (EC 3.1.1.3) from Propionibacterium acnes. J. Gen. Microbiol. 124, 393–401 (1981).

  22. 22.

    , & Interaction of Propionibacterium acnes with skin lipids in vitro. J. Gen. Microbiol. 139, 1745–1751 (1993).

  23. 23.

    , , , & Differences in the skin surface pH and bacterial microflora due to the long-term application of synthetic detergent preparations of pH 5.5 and pH 7.0. Results of a crossover trial in healthy volunteers. Acta Derm. Venereol. 70, 429–431 (1990).

  24. 24.

    , , & Effect of prolonged occlusion on the microbial flora, pH, carbon dioxide and transepidermal water loss on human skin. J. Invest. Dermatol. 71, 378–381 (1978).

  25. 25.

    The anaerobic microflora of the human body. Clin. Infect. Dis. 16, S175–S180 (1993).

  26. 26.

    , & Correlation of Propionibacterium acnes populations with the presence of triglycerides on nonhuman skin. Appl. Environ. Microbiol. 41, 1269–1270 (1981).

  27. 27.

    , , & Age-related changes in the resident bacterial flora of the human face. J. Invest. Dermatol. 65, 379–381 (1975).

  28. 28.

    The normal flora of the skin in different age groups. Br. J. Dermatol. 81, 248–258 (1969).

  29. 29.

    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).

  30. 30.

    & Bacterial colonisation of the skin of the newborn. J. Pathol. Bacteriol. 95, 115–122 (1968).

  31. 31.

    , , , & Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007).

  32. 32.

    Sex, constancy, and skin bacteria. Arch. Dermatol. Res. 272, 317–320 (1982).

  33. 33.

    , , & The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc. Natl Acad. Sci. USA 105, 17994–17999 (2008).

  34. 34.

    , & Gender-linked differences in human skin. J. Dermatol. Sci. 55, 144–149 (2009).

  35. 35.

    & Microbes and Health Sackler Colloquium: Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 16 Sep 2010 (doi:10.1073/pnas.1000087107).

  36. 36.

    et al. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect. Immun. 77, 2367–2375 (2009).

  37. 37.

    , , & The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6, e280 (2008).

  38. 38.

    , & The environment and the microbial ecology of human skin. Appl. Environ. Microbiol. 33, 603–608 (1977).

  39. 39.

    & The effect of UV-light on human skin microorganisms. Acta Derm. Venereol. 67, 69–72 (1987).

  40. 40.

    , , & Molecular analysis of human forearm superficial skin bacterial biota. Proc. Natl Acad. Sci. USA 104, 2927–2932 (2007).

  41. 41.

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

  42. 42.

    et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009). A comprehensive analysis of skin microbiota across 20 sites.

  43. 43.

    et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009). A comprehensive analysis of skin, gut and oral microbiota in the same individuals.

  44. 44.

    et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

  45. 45.

    et al. The human oral microbiome. J. Bacteriol. 192, 5002–5017 (2010).

  46. 46.

    , , & Defining the healthy 'core microbiome' of oral microbial communities. BMC Microbiol. 9, 259 (2009).

  47. 47.

    et al. Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J. 4, 962–974 (2010).

  48. 48.

    et al. Bacterial biota in the human distal esophagus. Proc. Natl Acad. Sci. USA 101, 4250–4255 (2004).

  49. 49.

    et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc. Natl Acad. Sci. USA 103, 732–737 (2006).

  50. 50.

    , , , & The microbiology of the human axilla and its relationship to axillary odor. J. Invest. Dermatol. 77, 413–416 (1981).

  51. 51.

    et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). An important study demonstrating the functional potential of the human microbiome.

  52. 52.

    et al. Reconstructing the early evolution of Fungi using a six-gene phylogeny. Nature 443, 818–822 (2006).

  53. 53.

    & Ecology. Barcoding of plants and fungi. Science 325, 682–683 (2009).

  54. 54.

    , & Analysis of Malassezia microbiota in healthy superficial human skin and in psoriatic lesions by multiplex real-time PCR. FEMS Yeast Res. 8, 460–471 (2008).

  55. 55.

    , , & Molecular analysis of fungal microbiota in samples from healthy human skin and psoriatic lesions. J. Clin. Microbiol 44, 2933–2941 (2006).

  56. 56.

    , , & Quantitation of major human cutaneous bacterial and fungal populations. J. Clin. Microbiol. 48, 3575–3581 (2010).

  57. 57.

    , & Medically important bacterial-fungal interactions. Nature Rev. Microbiol. 8, 340–349 (2010). This review describes the clinical and molecular characteristics of bacterium–fungus interactions that are relevant to human disease with a focus on Candida spp..

  58. 58.

    , , & Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br. J. Dermatol. 157, 474–481 (2007).

  59. 59.

    et al. Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea. J. Eur. Acad. Dermatol. Venereol. 15, 441–444 (2001).

  60. 60.

    Demodex mites: facts and controversies. Clin. Dermatol. 28, 502–504 (2010).

  61. 61.

    Demodex and skin infection: fact or fiction. Curr. Opin. Infect. Dis. 23, 103–105 (2010).

  62. 62.

    , , , & Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7, 509–515 (2010). An investigation of the preponderance of Merkel cell polyomavirus, and a methodology to isolate circular DNA viral genomes from human skin swabs.

  63. 63.

    & The coordinated response of the physical and antimicrobial peptide barriers of the skin. J. Invest. Dermatol. 131, 285–287 (2011).

  64. 64.

    , , & Cutaneous defence mechanisms by antimicrobial peptides. J. Invest. Dermatol. 125, 9–13 (2005).

  65. 65.

    Epithelial cells pay a Toll for protection. Nature Med. 10, 898–900 (2004).

  66. 66.

    & PI3K and negative regulation of TLR signaling. Trends Immunol. 24, 358–363 (2003).

  67. 67.

    et al. Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin. J. Invest. Dermatol. 130, 192–200 (2010).

  68. 68.

    et al. Staphylococcus epidermidis antimicrobial δ -toxin (phenol-soluble modulin-γ) cooperates with host antimicrobial peptides to kill Group A Streptococcus. PLoS ONE 5, e8557 (2010).

  69. 69.

    et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nature Med. 15, 1377–1382 (2009). This analysis demonstrated that products of a skin commensal can modulate the innate immune response.

  70. 70.

    et al. Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defence against bacterial skin infections. J. Invest. Dermatol. 130, 2211–2221 (2010).

  71. 71.

    et al. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J. Allergy Clin. Immunol. 112, 1195–1202 (2003).

  72. 72.

    et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J. Immunol. 171, 3262–3269 (2003).

  73. 73.

    et al. Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin. J. Invest. Dermatol. 129, 2795–2804 (2009).

  74. 74.

    et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 347, 1151–1160 (2002).

  75. 75.

    et al. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J. Invest. Dermatol. 125, 1163–1173 (2005).

  76. 76.

    , , & A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis. Br. J. Dermatol. 145, 886–890 (2001).

  77. 77.

    , , & Prolonged effects of antidandruff shampoos — time to recurrence of Malassezia ovalis colonization of skin. Int. J. Cosmet. Sci. 19, 111–117 (1997).

  78. 78.

    , & Role of microorganisms in dandruff. Arch. Dermatol. 112, 333–338 (1976).

  79. 79.

    , , , & Skin diseases associated with Malassezia species. J. Am. Acad. Dermatol. 51, 785–798 (2004).

  80. 80.

    & The role of Propionibacterium acnes in acne pathogenesis: facts and controversies. Clin. Dermatol. 28, 2–7 (2010).

  81. 81.

    , & Activation of complement — a mechanism for the inflammation in acne. Br. J. Dermatol. 101, 315–320 (1979).

  82. 82.

    , & Complement activation in acne vulgaris: consumption of complement by comedones. Infect. Immun. 26, 183–186 (1979).

  83. 83.

    , , , & Inflammatory events are involved in acne lesion initiation. J. Invest. Dermatol. 121, 20–27 (2003).

  84. 84.

    Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology 211, 193–198 (2005).

  85. 85.

    & Cytotaxin production by comedonal bacteria (Propionibacterium acnes, Propionibacterium granulosum and Staphylococcus epidermidis). J. Invest. Dermatol. 74, 36–39 (1980).

  86. 86.

    & Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes. Inflammation 4, 261–269 (1980).

  87. 87.

    , & Acne is not associated with yet-uncultured bacteria. J. Clin. Microbiol. 46, 3355–3360 (2008).

  88. 88.

    & Staphylococcal infections in patients with atopic dermatitis. Arch. Dermatol. 113, 1383–1386 (1977).

  89. 89.

    , & Staphylococcus aureus in the lesions of atopic dermatitis. Br. J. Dermatol. 90, 525–530 (1974).

  90. 90.

    , , , & Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics 123, e808–e814 (2009).

  91. 91.

    et al. Impairment of skin barrier function in NC/Nga Tnd mice as a possible model for atopic dermatitis. Br. J. Dermatol. 144, 12–18 (2001).

  92. 92.

    et al. Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proc. Natl Acad. Sci. USA 103, 8816–8821 (2006).

  93. 93.

    et al. Microbial diversity in chronic open wounds. Wound Repair Regen. 17, 163–172 (2009).

  94. 94.

    et al. Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol. 8, 43 (2008).

  95. 95.

    et al. Evaluation of the bacterial diversity of Pressure ulcers using bTEFAP pyrosequencing. BMC Med. Genomics 3, 41 (2010).

  96. 96.

    et al. Community analysis of chronic wound bacteria using 16S rRNA gene-based pyrosequencing: impact of diabetes and antibiotics on chronic wound microbiota. PLoS ONE 4, e6462 (2009).

  97. 97.

    , & Microbiology of burn wound infections. J. Craniofac. Surg. 19, 899–902 (2008).

  98. 98.

    et al. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defence response. Proc. Natl Acad. Sci. USA 107, 14799–14804 (2010). This study showed that a selective shift in microbiota is associated with an altered innate immune response.

  99. 99.

    et al. Foreign body infections due to Staphylococcus epidermidis. Ann. Med. 41, 109–119 (2009).

  100. 100.

    Staphylococcus epidermidis — the 'accidental' pathogen. Nature Rev. Microbiol. 7, 555–567 (2009).

  101. 101.

    et al. The NIH Human Microbiome Project. Genome Res. 19, 2317–2323 (2009). A detailed description of the Human Microbiome Project and its objectives.

  102. 102.

    et al. Staphylococcus epidermidis esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010). An important paper demonstrating the mechanism by which S. epidermidis inhibits S. aureus colonization of the nare.

  103. 103.

    , , & Empirical and theoretical bacterial diversity in four Arizona soils. Appl. Environ. Microbiol. 68, 3035–3045 (2002).

  104. 104.

    , & Wound microbiology and associated approaches to wound management. Clin. Microbiol. Rev. 14, 244–269 (2001).

  105. 105.

    et al. Use of molecular techniques to study microbial diversity in the skin: chronic wounds reevaluated. Wound Repair Regen. 9, 332–340 (2001).

  106. 106.

    & Identifying microbial diversity in the natural environment: a molecular phylogenetic approach. Trends Biotechnol. 14, 190–197 (1996).

Download references

Acknowledgements

We thank H. Kong and E. Hobbs for critical reading of the manuscript and J. Fekecs and D. Leja for graphical assistance. E.A.G. is supported by a Pharmacology Research Associate Training Fellowship, US National Institute of General Medical Sciences. This work was supported by the US National Human Genome Research Institute Intramural Research Program and the US National Institutes of Health Common Fund AR057504.

Author information

Affiliations

  1. Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892–4442, USA.

    • Elizabeth A. Grice
    •  & Julia A. Segre

Authors

  1. Search for Elizabeth A. Grice in:

  2. Search for Julia A. Segre in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Julia A. Segre.

Glossary

Keratinocyte

The predominant cell type of the epidermis. Keratinocytes produce keratin as they terminally differentiate into the squames of the stratum corneum.

Squame

An enucleated, dead, squamous keratinocyte that is shed from the stratum corneum.

Sebum

The oily, lipid-containing substance that is secreted by the sebaceous glands of the skin. Sebaceous glands are connected to the hair follicle and form the pilosebaceous unit. Sebum protects and emolliates the skin and hair.

16S ribosomal RNA metagenomic sequencing

Genomic analysis of 16S ribosomal RNA phylotypes from DNA that is extracted directly from bacterial communities in clinical or environmental samples, a process that circumvents culturing.

Microbiome

All of the genetic material of a microbial community sequenced together.

Phylotype

A taxon-neutral way to describe organisms based on their phylogenetic relationships to other organisms. Phylotypes are determined by comparing 16S ribosomal RNA gene sequences. A common threshold used to define species-level phylotypes is 97% sequence identity of the 16S rRNA gene sequence.

Whole-genome shotgun metagenomic sequencing

Genomic analysis of DNA that is extracted directly from a clinical or environmental sample and whole-genome shotgun (WGS) sequenced to represent the full microbiome.

Pattern recognition receptor

(PRR). A receptor present on the surface of keratinocytes and other cells of the innate immune system that recognizes microorganism-specific molecules (for example, lipopolysaccharide and flagellin).

Pathogen-associated molecular pattern

(PAMP). A molecule that is associated with a pathogen and recognized by a pathogen recognition receptor. Examples include lipopolysaccharide, flagellin, lipoteichoic acid, double-stranded RNA, peptidoglycan and unmethylated CpG motifs.

Atopic dermatitis

(AD). A type of eczema characterized by red, flaky, itchy skin, typically affecting the inner elbows and behind the knees. It is often associated with other atopic diseases such as allergic rhinitis, hay fever and asthma

Seborrhoeic dermatitis

An inflammatory, hyperproliferative skin condition characterized by red, flaky, skin often affecting sebaceous areas of the face, scalp and trunk. Commonly known as dandruff.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrmicro2537

Further reading