The Skin Microbiome in Health and Disease – Humans, Dogs and their Relationship
Aline Rodrigues Hoffmann, DVM, PhD, Diplomate ACVP
Department of Veterinary Pathobiology, College of Veterinary Medicine,
Texas A&M University, College Station, TX
arodrigues@cvm.tamu.edu
Introduction
The skin is an ecosystem, colonized by a wide variety of microorganisms including
bacteria, fungi and viruses, which often live in symbiosis with their host.4 The normal skin
microbiota is necessary for optimal skin fitness, modulating the innate immune response, and
preventing colonization of potentially pathogenic microorganisms.13 An imbalance in these
residing microorganisms may result in damage to its host. In many skin conditions, it is still
unclear if the changes in the cutaneous microbiota are a causal role of skin diseases or a result of
skin bacterial dysbiosis.15
The understanding of the microorganisms inhabiting the skin of humans and domestic
animals has, until recently, been based on conventional microbiology techniques such as culture
and biochemical methods.14 Molecular studies using sequencing of bacterial 16S rRNA gene
have revealed that the different body sites of the skin surface of humans is inhabited by a highly
diverse, and variable microbiota that was previously not demonstrated by culture-based
methods.3,4,6,8 The 16S rRNA gene, which is present in all bacteria and archaea, but not in
eukaryotes, contains species-specific hypervariable regions, which allows taxonomic
classification of bacterial species.5
The human skin microbiome
The skin of humans is inhabited by a highly diverse microbiome that varies between
different body sites. It has been demonstrated that the microbiome from similar skin locations
from different people are more likely to be more closely related compared with different skin
locations from the same individual. The hair follicles, temperature, pH, moisture, environmental
contact, and contact with mucous membranes are considered some of the factors associated with
variability of the bacterial abundance and distribution in the human skin.4,12 Studies evaluating
the skin microbiome in humans have described that Propionibacterium spp. predominate in
sebaceous areas, Staphylococcus spp. and Corynebacterium spp. colonize moist areas, and gram
negative organisms are more likely to colonize dry skin areas such as the forearm or leg.4
Age is also considered one of the factors that can influence the skin microbiome, with
infants having a different skin microbiome than adults. For instance, it is described that the
relative abundances of Staphylococcus spp., and Streptococcus spp. in the skin decrease with
age, and that the abundance of Propionibacterium spp. inhabiting the forehead increases with
age.1 The composition of the skin microbiome in humans can also be altered during activities
involving human to human contact. One example was the evaluation of the skin microbiome
after participation in a sport involving skin to skin contact.9
The skin microbiome also extends beyond the epidermal surface. By utilizing 16s rRNA
bacterial genomic analysis combined with detection techniques in tissues, such as gram stain,
immunofluorescence and in situ hybridization, it has been demonstrated that the dermis and
subcutaneous tissues, previously thought to be sterile, actually also harbor a distinct microbial
community.10
In children with atopic dermatitis (AD), marked reduction in microbial diversity,
followed by increased abundance of cutaneous S. aureus is described during skin flares.7 It is
described that increases in the abundance of Staphylococcus and reductions in microbial
diversity precede an increase in the severity of AD. Besides S. aureus, the skin commensal S.
epidermidis also increased during non-treated flares. It was proposed that this commensal
relationship could possibly enhance common resistance to antimicrobial peptides or enhance
binding to exposed extracellular matrix proteins in inflamed AD skin. In these atopic children,
antimicrobial or anti-inflammatory medications (hypochlorite baths) decreased, but did not
eliminate, S. aureus. Interestingly, the changes in the microbial diversity during flares were
reversed even before clinical improvement was seen.
Genomic analysis has also been used to characterize the fungal diversity in human skin
(mycobiome).2 By evaluating the fungal variable regions present in the 18S rRNA, it was shown
that the genus Malassezia predominated in all skin regions, with 11 of the 14 known Malassezia
species being identified among skin sites. The plantar heel was the most diverse site with higher
representation of differen fungi genera, including Malassezia spp., Aspergillus spp.,
Cryptococcus spp., Rhodotorula spp. and Epicoccum spp.
The skin microbiome in humans cohabiting with dogs
In a very interesting study, Song et al.12 evaluated and compared the skin, oral and fecal
microbiome of human families and their dogs. They demonstrated that dog ownership influenced
the diversity of the skin microbiome in adult people, with individuals with dogs sharing a more
similar microbiome than those who do not own dogs. Adult individuals that cohabit with dogs,
also had higher microbiome diversity. Similar to cohabiting humans, dogs that live with humans
also shared a more similar microbiome than dogs who do not live with humans. When the oral
and fecal microbiome was compared between these families, dog ownership did not influence the
diversity of the microbiome in these individuals. Interestingly, ownership of indoor cats did not
influence the diversity of the skin microbiome and taxa shared between cohabiting adult
individuals.
The skin microbiome in healthy dogs
We recently evaluated the diversity of the skin microbiome in different cutaneous and
mucocutaneous regions in healthy dogs.11 The bacterial 16S rRNA gene was sequenced from
skin swabs using a large scale DNA sequencing system (454 pyrosequencing). Similar to
previous studies in humans, sequence analysis revealed high individual variability between
samples collected from healthy dogs. A large number of previously uncultured or rarely isolated
microbes were identified in the skin of dogs, demonstrating that the skin of dogs is inhabited by
much more rich and diverse microbial communities than was previously thought, using culture
methods. Each skin site from each dog evaluated here was inhabited by a variable and unique
microbiome, with significant individual variability between samples from different dogs and
between different skin sites. Higher species richness and diversity were observed in the haired
skin (axilla, groin, periocular, pinna, dorsal nose, interdigital, lumbar) when compared to
mucosal surfaces or mucocutaneous junctions (lips, nose, ear, and conjunctiva) (Figure 1). The
nostril and conjunctiva were the skin regions that had the lowest species richness and diversity;
whereas the axilla and dorsal aspect of the nose had higher species richness and diversity. On
average, around 300 different bacterial genera were identified on the dorsal nose.
The most abundant phylum identified in the different regions of skin and mucosal surface
were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. The family
Oxalobacteraceae (phylum Proteobacteria) was the most abundant group in most samples from
haired skin and mucocutaneous junctions, whereas the family Moraxellaceae was the most
abundant in the nostril.
The skin microbiome in allergic dogs
In addition to evaluating the skin microbiome in healthy dogs, we also evaluated the skin
microbiome in allergic dogs.11 The haired skin and nostril of dogs with allergic skin disease
showed lower number of observed bacterial species and diversity when compared to the same
skin sites (axilla, groin, and interdigital skin) of healthy dogs (Figure 2). Significant differences
were observed at different phylogenic levels when comparing allergic versus healthy dogs
(Figure 3). One major difference was the abundance of Ralstonia spp. (Betaproteobacteria) in the
skin of healthy dogs, whereas significantly lower proportions of this bacteria was observed in the
allergic dogs. Bacteria genera identified in the skin of allergic dogs included Alicyclobacillus
spp., Bacillus spp., Corynebacterium spp. Staphylococcus spp., and Sphingomonas spp.
Conclusion and Future Directions
Before we are able to draw any definitive conclusions regarding the skin microbiome
inhabiting the skin of healthy and allergic dogs, additional studies are needed to evaluate a larger
number of individuals, and serial studies are needed to evaluate the shifts that occur in the skin
microbiome in dogs and other animals during disease states.
The ability to examine the dynamics of bacterial communities is one of the major
advantages of microbial genomics. The host and microbial interactions likely play an important
role in skin health, susceptibility to infection, and clinical variability and treatment response of
certain individuals predisposed to skin disease. Examining these bacterial interactions could
allow us to better understand how these communities contribute to health and diseases, and
perhaps identify successful treatment for skin diseases and develop new therapies that enhance
beneficial microbes, ultimately reducing the use of systemic antibiotics (a known risk factor in
the development of bacterial resistance).
Figure 1. Number of observed bacterial
species in the haired skin and non-haired
skin/ mucocutaneous junctions in healthy
dogs (p<0.0001).
Figure 2. Number of observed bacterial
species in the haired skin (axilla, groin, and
interdigital skin) of allergic (A) versus
healthy (H) dogs (p<0.05).
Figure 3. Average of most common bacterial phyla in the axilla, groin, and nostril of allergic
versus healthy dogs. The group “Other phyla” includes 12 phyla that each were present in only
low abundance.
Literature Cited
1 Capone KA, Dowd SE, Stamatas GN, Nikolovski J: Diversity of the human skin microbiome
early in life. J Invest Dermatol 2011:131(10):2026-2032.
2 Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, et al.: Topographic diversity of
fungal and bacterial communities in human skin. Nature 2013:498(7454):367-370.
3 Grice EA, Kong HH, Renaud G, Young AC, Program NCS, Bouffard GG, et al.: A diversity
profile of the human skin microbiota. Genome Res 2008:18(7):1043-1050.
4 Grice EA, Segre JA: The skin microbiome. Nat Rev Microbiol 2011:9(4):244-253.
5 Hugenholtz P, Pace NR: Identifying microbial diversity in the natural environment: a
molecular phylogenetic approach. Trends Biotechnol 1996:14(6):190-197.
6 Kong HH: Skin microbiome: genomics-based insights into the diversity and role of skin
microbes. Trends Mol Med 2011:17(6):320-328.
7 Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, et al.: Temporal shifts in the
skin microbiome associated with disease flares and treatment in children with atopic
dermatitis. Genome Res 2012:22(5):850-859.
8 Kong HH, Segre JA: Skin microbiome: looking back to move forward. J Invest Dermatol
2012:132(3 Pt 2):933-939.
9 Meadow JF, Bateman AC, Herkert KM, O'Connor TK, Green JL: Significant changes in the
skin microbiome mediated by the sport of roller derby. PeerJ 2013:1:e53.
10 Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL: The microbiome
extends to subepidermal compartments of normal skin. Nat Commun 2013:4:1431.
11 Rodrigues Hoffmann A, Patterson AP, Diesel A, Lawhon SD, Li HJ, Elkins C, et al.: The
Skin Microbiome in Healthy and Allergic Dogs. Manuscript submitted for publication.
12 Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D, et al.:
Cohabiting family members share microbiota with one another and with their dogs. Elife
2013:2:e00458.
13 Wanke I, Steffen H, Christ C, Krismer B, Gotz F, Peschel A, et al.: Skin commensals amplify
the innate immune response to pathogens by activation of distinct signaling pathways. J
Invest Dermatol 2011:131(2):382-390.
14 Whitman WB, Coleman DC, Wiebe WJ: Prokaryotes: the unseen majority. Proc Natl Acad
Sci U S A 1998:95(12):6578-6583.
15 Zeeuwen PL, Boekhorst J, van den Bogaard EH, de Koning HD, van de Kerkhof PM,
Saulnier DM, et al.: Microbiome dynamics of human epidermis following skin barrier
disruption. Genome Biol 2012:13(11):R101.