Chinese Medical Journal January 5, 2018 V olume 131 Issue 1 95Perspective [613017]

Chinese Medical Journal ¦ January 5, 2018 ¦ V olume 131 ¦ Issue 1 95Perspective
IntroductIon
Psoriasis is characterized by raised, scaly, well‑demarcated,
erythematous oval plaques.[1] Although studies have
revealed that disruption of immune tolerance and excessive
production of inflammatory factors play important roles
in the pathogenesis of psoriasis, the exact mechanism
is still not clear.[2] Previous studies have shown that the
concordance rate of monozygotic twins with psoriasis is
greater than that of dizygotic twins,[3,4] with genetic factors
underpinning 66–90% of the variation in risk of developing
psoriasis.[5] These studies reveal not only the genetic
influence on psoriasis but also that nongenetic factors are
important in the pathogenesis of psoriasis.
Each one of us is colonized by some 100 trillion bacteria
that reside in our intestines, mouth, nose, genitals, and
skin.[6] As a critical barrier to the outside world, human skin
is the body’s largest and most exposed organ. Human
skin closely interacts with the exterior environment, and
the commensal microbiota at the skin play an important
role in maintaining the function of skin barrier.[6] An
assemblage of microorganisms, including bacteria, fungi,
viruses, and arthropods, colonize the human skin and
together form the skin microbiome.[7] The skin microbiome
plays an important role in maintaining human health
through inhibition of invasion by pathogens, formation of
biofilms, and production of antibacterial peptides. Recent
studies indicate that the composition of the human skin
microbiome is closely related to many diseases including
atopic dermatitis,[8] psoriasis,[9] and acne vulgaris.[10] In
this review, we will focus on the relationship between
the skin microbiome and the function of the skin barrier,
the microbiome changes in psoriasis, and the possible
pathogenic mechanisms involved.skIn MIcrobIoMe and the skIn barrIer
Because skin is protective against physical, biological, and
chemical stress, it is considered to be an effective barrier
between the body and the environment.[11] The skin consists
of epidermis, dermis, and hypodermis. Epidermis is stratified
into four layers according to the stage of keratinocyte
differentiation: stratum corneum, stratum granulosum,
stratum spinosum, and stratum basale.[12] The skin barrier is
formed by differentiating keratinocytes and is continuously
renewed. Previous studies have showed that the stratum
corneum and epidermal tight junctions are two of the main
elements in the barrier function of the skin.[13] The microbial
ecology of human skin is complex and may play an important
role in diseases. Studies focusing on healthy volunteers
have demonstrated that Staphylococcus , Micrococcus ,
Corynebacterium , Brevibacteria, Propionibacteria, and
Acinetobacter species regularly reside in normal skin.[14] The
most common fungal species present on normal human skin
are Malassezia .[15] A study of 11 body locations (the forehead,
left and right axillae, left and right inner elbows, left and
right forearms, left and right forelegs, and behind the left
and right ears) from eight healthy adult participants showed
that Malassezia accounts for up to 80% of the fungi on the
skin.[16] Both environmental and host factors can affect the
skin microbiome such as climate, body location, age, and
gender.[17] For site‑specific composition, the skin microbiome Skin Microbiome: An Actor in the Pathogenesis of
Psoriasis
Wen‑Ming Wang, Hong‑Zhong Jin
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,
Beijing 100730, China
Key words: Inflammatory Diseases; Psoriasis; Skin Microbiome
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DOI:
10.4103/0366‑6999.221269Address for correspondence: Dr. Hong‑Zhong Jin,
Department of Dermatology, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing 100730, China
E‑Mail: jinhongzhong@263.net
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© 2017 Chinese Medical Journal ¦ Produced by Wolters Kluwer ‑ Medknow
Received: 17‑08‑2017 Edited by: Li‑Min Chen
How to cite this article: Wang WM, Jin HZ. Skin Microbiome: An Actor
in the Pathogenesis of Psoriasis. Chin Med J 2018;131:95‑8.

Chinese Medical Journal ¦ January 5, 2018 ¦ V olume 131 ¦ Issue 1 96was found to be quite different across the population.
However, when skin sites with bilateral symmetry were
compared, the intraindividual variability of the skin
microbiota had a high level of conservation.[14,18]
Staphylococcus has been associated with impaired wound
healing in both clinical and laboratory models. Mullikin
et al. found that a longitudinal selective shift of microbiota
coincided with aberrant expression of innate immunity
genes in diabetic mice. Moreover, they detected aberrant
expression of innate immunity genes associated with the
significantly enriched cutaneous host defense response and
increased Staphylococcus abundance.[19] Zeeuwen et al.
showed that Propionibacterium was the dominant genus in
the early recolonization phase during healing of superficial
wounds.[20]
skIn MIcrobIoMe and skIn InflaMMatIon
Previous studies have showed that skin microbiota is
involved in the balance of cutaneous inflammation and
anti‑inflammatory processes. Germ‑free (GF) mice have
reduced interferon‑ γ produced by αβ T‑cells and reduced
interleukin (IL)‑17A produced by αβ and γδ T‑cells but have
an increase in Foxp3+ Treg cells in the skin compared with
specific pathogen‑free (SPF) mice. In addition, application
of Staphylococcus to the epidermidis of GF mice can restore
the production of IL‑17A by T‑cell receptor β+ (TCRβ+)
T cells in the skin. MyD88 and IL‑1R1 knockout mice
have reduced IL‑17A production from TCR β+ cells in the
skin.[21,22] Together, these data suggest that skin commensals
are important in the inflammatory T‑cell response.
Filaggrin plays a crucial role in maintenance of the
skin barrier. In lesioned skin from filaggrin‑deficient
flaky tail (Flgft/ft) mice raised in SPF conditions, dermal
eosinophils, neutrophils, and expression of IL‑17A
mRNA were significantly increased in comparison with
GF Flgft/ft mice.[23,24] Lai et al. found that Staphylococcus
epidermidis can suppress inflammatory cytokine release from
keratinocytes through a TLR3‑dependent mechanism.[25]
skIn MIcrobIoMe and skIn IMMunIty
Both the innate and adaptive immune systems play roles
in the immune function of skin.[26] The innate immune
system is considered as a sentinel for detecting invasion
by microorganisms. By releasing antimicrobial peptides,
chemotactic proteins, and cytokines, keratinocytes,
Langerhans cells, mast cells, dendritic cells, and macrophages
provide an early warning system.[27,28] Using T‑ and B‑cells
expressing antigen‑specific receptors, the adaptive immune
system provides more broad and flexible response to
pathogens. It is regarded as a means for providing memory
of previous pathogen encounters. At the skin interface, this
process involves three stages: increasing the efficiency of
naïve T‑cells that are exposed to antigens, targeting the
effector response to the most appropriate tissue site, and
expanding coverage to other tissues.[29]It has been proposed that the skin microbiome greatly
impacts upon human immune functions. However, the
mechanisms associated with this role have remained elusive.
The mechanisms probably include inhibiting the growth
of pathogenic microbes, enhancing host innate immunity,
and educating adaptive immunity.[15] S. epidermidis is
a common commensal bacterium of the skin, whereas
Staphylococcus aureus is a human pathogen. A study
conducted by Iwase et al. showed that S. epidermidis
can inhibit S. aureus biofilm formation.[30] In another
study, after inoculation of the upper arm, swabs were
taken at multiple time points for Haemophilus ducreyi .
Papules either spontaneously resolved or progressed to
pustules, with the microbiomes differing between the
two groups. Proteobacteria , Bacteroidetes , Micrococcus ,
Corynebacterium , Paracoccus , and Staphylococcus species
were more abundant at pustule‑forming sites, whereas
resolved sites had a greater abundance of Actinobacteria
and Propionibacterium species.[31] Shu et al. demonstrated
that Propionibacterium acnes can inhibit the growth of
methicillin‑resistant S. aureus.[32] Together, these findings
illustrate a crucial role for commensal bacteria in the host
immune defense against pathogens.
skIn MIcrobIoMe and skIn psorIasIs
Psoriasis is a chronic inflammatory skin disease and a
genetically disposed immune disorder. Psoriasis can be
provoked or exacerbated by specific pathogens including
bacteria (S. aureus and Streptococcus pyogenes ), viruses
(human papillomavirus and endogenous retroviruses), and
fungi ( Malassezia and Candida albicans ).[33] Alekseyenko
et al . showed that the abundances of Corynebacterium ,
Propionibacterium , Staphylococcus , and Streptococcus
were significantly increased in psoriatic plaques.[34] Fahlén
et al. found that streptococci were the most common genera
in both normal and psoriasis skin, whereas staphylococci
and Propionibacteria were significantly lower in psoriasis
compared with control limb skin.[35] Consistent with the
former, Gao et al. revealed that Propionibacterium species
were less abundant in psoriasis than in normal controls.[9] In
another study, a reduction in Firmicutes and an increase in
Proteobacteria were found in psoriatic patients.[36] Liew et al.
found that Firmicutes were significantly overrepresented
in psoriatic lesions in comparison with uninvolved skin
in patients and in healthy controls. Actinobacteria and
Propionibacterium were significantly underrepresented in
the psoriatic lesion samples.
Using pyrosequencing of fungal rRNA from 12 psoriatic
patients and 12 healthy controls, Takemoto et al. showed
that Malassezia was the most abundant fungus in both
groups. However, the level of Malassezia colonization in
psoriasis patients was lower than that in healthy controls. In
general, the fungal microbiome of the psoriasis group was
more diverse in comparison with the healthy controls.[37]
Supporting the former study, Paulino et al.[38] found that
Malassezia restricta was the most abundant species in six

Chinese Medical Journal ¦ January 5, 2018 ¦ V olume 131 ¦ Issue 1 97healthy and two psoriatic skin samples; however, they
found no significant difference in the microbiota of the
two skin types. Horton et al.[39] found that infections are
associated with the development of pediatric psoriasis,
but antibiotics use does not contribute substantially to
that risk. Reduced bacterial biodiversity was noted in
psoriatic patients. Xanthomonadaceae , which belongs to
the Proteobacteria phylum, were associated with clinical
improvement of psoriasis after a 3‑week balneotherapy
treatment.[40]
Although further studies are required to establish an
association between the cutaneous microbiome and psoriasis,
current research suggests that the microbiome in patients
with psoriasis is distinct from that of healthy controls.
In conclusions, the skin microbiome is closely associated
with the functions of the skin barrier and immune system.
Advances in sequencing technology have allowed us to
characterize the skin microbiome and how it is altered in
psoriasis. Future studies investigating the crosstalk between
the human skin microbiome and the immune system, and
their influences on psoriasis, will enhance our understanding
of the occurrence, development, and relapse of psoriasis.
Because skin is relatively accessible, further research and
an improved understanding of the skin microbiome should
lead to diagnostic and therapeutic applications.
Financial support and sponsorship
This study was supported by grant from the Capital Health
Development Research Fund of China (No. 2016‑2‑4018).
Conflicts of interest
There are no conflicts of interest.
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