Download Mayo Clinic Grand Rounds

The Skin Microbiome
Yoon K. Cohen, D.O.
Hot Spots in Dermatology
August 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
Bacteria Commonly Found on Skin
 Staphylococcus epidermidis
 Staphylococcus aureus
 Corynebacterium spp.
 Propionibacterium acnes
S. Epidermidis
 Pathogen
 Frequent cause of nosocomial
infections
 Immunocomprised patients
 Indwelling devices
 Commensal
 Major skin inhabitant
 Produce antibacterial products
 Bacteriocins (epidermin, epilancin
K7, Pep5, staphlococcin 1580)
A clump of Staphylococcus
epidermidis bacteria
S. Aureus
 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)
Corynebacterium spp.
 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
Propionibacterium acnes
 Pathogen
 Associated with folliculitis, systemic infections and acnes
 Commensal
 Produce bacteriocin-like compounds with activity against
bacteria, yeast and molds
Other Microbes Commonly Found on Skin
 Malassezia spp.
 Demodex mites
 Human papillomavirus (HPV)
Identifying Fungi and Viruses
 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
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