The Skin Microbiome

Yoon K. Cohen, D.O.Hot Spots in DermatologyAugust 18, 2013

Objectives

Human Microbiome Project

Introduction of Skin Microbiome

Factors Contributing to Variation in the Skin Microbiome

Topographical Distribution of Microbes

Microbes Commonly Found on Skin

The Skin Microbiome and Diseases

Human Microbiome Project

250 Healthy Volunteers

5 Sites Nasal passage Oral cavities GI Urogenital tract Skin

16S ribosomal RNA genomic sequening on 11,174 samples Conserved regions a binding

site for PCR primer Hypervariable regions

taxonomic classification

Chen YE, et al. The skin microbiome: Current perspectives and futures challenges. J Am Acad Dematol. 2013; 69:143-155

Skin Microbiome

Microbiology and dermatology have been intimately related

The cutaneous surface is inhabited by myriad bacteria, fungi, and viruses. Now we begin to understand how these microbial communities impact human health and disease

The skin microbiota plays a vital role in educating the immune system as the cutaneous innate and adaptive immune reponses can modulate the skin microbiota

Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

Microbiome and skin immunology

Chen YE, et al. The skin microbiome: Current perspectives and futures challenges. J Am Acad Dematol. 2013; 69:143-155

Skin Microbiome

Three major questions What microbes are present

on the skin surface? How does microbial

diversity contribute to health and disease states?

How do dermatologic practices alter microbial diversity?

Kong HH, Segre JA. Skin Microbiome: Looking Back to Move Forward. J Invest Dermatol. 2011;132:933-39

Factors Contributing to Variation in the Skin Microbiome

Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

Topographical Distribution of Bacteria on Skin Sites

Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

Composition of a Single Metagenome

Chen YE, et al. The skin microbiome: Current perspectives and futures challenges. J Am Acad Dematol. 2013; 69:143-155

Interpersonal Variation of the Skin Microbiome

This chart demonstrates that skin microbial variation is more dependent on the site than on the individual. Bars represents the relative abundance of bacterial taxa as determined by 16S ribosomal RNA sequencing

Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

Temporal diversity of the microbiome

Oh et al, Shifts in human skin and nares microbiota of healthy children and adults. Genome Medicine. 2012

Staphylococcus epidermidis

Staphylococcus aureus

Corynebacterium spp.

Propionibacterium acnes

Bacteria Commonly Found on Skin

Pathogen Frequent cause of nosocomial

infections Immunocomprised patients Indwelling devices

Commensal Major skin inhabitant Produce antibacterial products

Bacteriocins (epidermin, epilancin K7, Pep5, staphlococcin 1580)

S. Epidermidis

A clump of Staphylococcus epidermidis bacteria

Pathogen Frequent cause of infections (self-limited to invasive) Methicillin-resistance is a healthcare problem

Phenol-soluble modulins (PSMs) produced in high levels by CA-MRSA Streptococcus pyogenes is sensitive to S. aureus PSMs, which may

partically explain CA-MRSA dominance

Commensal Asymptomatic nasal colonizers

20% permanently colonized 30-50% transiently colonized S. aureus preferentially hemolyzes human

blood to utilizes iron from heme to promote proliferation Can produce bacteriocin (staphylococcin 462)

S. Aureus

Pathogen Diphtheroids

+/- C. dephtheriae Part of normal skin flora C. minutissimum (erytherasma) and C.

tenuis (trichomycosis) Risk factors for infections

Immunocompromised patients Skin barrier defects

Commensal Prevents oxidative damage by producing

superoxide dismutase Produce bacteriocin-like compounds

Corynebacterium spp.

Pathogen Associated with folliculitis, systemic infections and acnes

Commensal Produce bacteriocin-like compounds with activity against

bacteria, yeast and molds

Propionibacterium acnes

Malassezia spp.

Demodex mites

Human papillomavirus (HPV)

Other Microbes Commonly Found on Skin

Fungi Similar strategy can be used

to classify the 18S rRNA or the intervening sequence (ITS) of fungi

Viruses De-novo sequencing Challenging what to use for

control for DNA or RNA viruses Currently resequencing the

human genome to identify viral associated disease

Once you find them, finding them again is PCR-based

Identifying Fungi and Viruses

Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

Relative abundance of fungal genera and Malassezia species at different human skin sites.

Fungal diversity of individual body sites of healthy volunteers (1–10) was taxonomically classified at the genus level, with further resolution of Malassezia species.

Findley et al. Topographic diversity of fungal and bacterial communities in human skin. Nature. June 2013

Skin Diseases Associated with Dysbiosis

Gallo RL, Nakatsuji T. Microbial Symbiosis with the innate immune Defense System of the Skin. J invest Dermatol. 2011

Conclusions

Skin Microbiome How molecular approaches allow us to better understand the relationship between skin microbiome and human health & disease states

Currently active ongoing research for skin microbiome under NIH Human Microbiome Project

Future Therapeutic Options The impact of repeated use of topical/systemic antimicrobial therapies

Mainstay of dermatologic practice Associated risks are not fully understood

Alternative therapies Probiotic microbial organisms Antimicrobial chemicals derived from microorganisms or humans

References

1. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011; 9: 244-53

2. Kong HH, Segre JA. Skin Microbiome: Looking Back to Move Forward. J Invest Dermatol. 2012; 132: 933-39

3. Capone KA. Dowd SE, Stamatas GN, et al. Diversity of the Human Skin Microbiome Early in Life. J invest Dermatol. 2011; 131: 2026-32

4. Gallo RL, Nakatsuji T. Microbial Symbiosis with the innate immune Defense System of the Skin. J invest Dermatol. 2011; 131: 1974-80

5. Gaspari AA, et al. Chapter 9. “Antimicrobial Peptides”. Clinical and Basic Immunodermatology. Springer. London. 2009

6. Zimmer C. Tending the Body’s Microbial Garden. The New York Times. June 18, 2012

7. Specter M. Germs Are Us. The New Yorker. October 22, 2012

8. Gorman C. Explore the Human Microbiome. Scientific American. May 15, 2012

The Sebago Lake in Maine, May 27th, 2012