506 JOURNAL OF COSMETIC SCIENCE
Up-regulation of HBD2 is believed to play an important role in cutaneous immune
defense, and expression of this AMP appears to be localized to the upper Malpighian layer
of the epidermis and stratum corneum.107,108 S. epidermidis is a good inducer of HBD2 and
is tolerant to it, which enables S. epidermis to colonize skin. Streptococcus pyogenes is known to
be a poor/variable inducer of HBD2, which means that S. pyogenes can reside on skin and
mucous membranes without stimulating skin cells to release substantial amounts of HBD2.
However, S. pyogenes is reported to be significantly more sensitive to killing by HBD2 than
S. epidermidis.107 Consequently, the growth of S. epidermidis on skin up-regulates HBD2
which helps limit S. pyogenes colonization of skin.
Phenol-soluble modulins (PSMs) are AMPs which are small peptides with an amphipathic
α-helical structure and strong surfactant-like properties. PSMs are produced by most
staphylococci and can induce the production of proinflammatory cytokines, recruit, activate,
and lyse neutrophils to help staphylococci evade destruction by these neutrophils. For
example, PSMs facilitate the detachment and dissemination of staphylococcal biofilms.66
PSMα elicits a keratinocyte Myd88 signaling response that drives an IL-17-mediated skin
inflammatory response to S. aureus colonization of skin, and PSMε enhances production
of IL-8—neutrophil chemotactic factor—a proinflammatory mediator that recruits and
activates neutrophils to kill competing microorganisms.109-111
The normally functioning skin microbiome assists the body’s immune barrier however,
dysbiosis (i.e., disruption of the microbiome with changes composition and/or metabolic
activities) may lead to inflammatory skin disorders.112 For example, C. acnes is involved
directly or indirectly in the pathogenesis of acne vulgaris. The free fatty acids and porphyrins
produced by C. acnes cause skin inflammation.68,82,113 S. epidermidis, and to a lesser extent,
S. aureus normally colonize human skin without any negative health effects, but these
bacteria may worsen atopic dermatitis (AD) in some patients. It is not known whether over-
colonization by staphylococci in AD is the cause or the consequence of inflammation.74,114,115
Malassezia yeasts are residents of healthy skin, but Malassezia spp. may cause dandruff
and seborrheic dermatitis in susceptible individuals.116 The microbiome of patients with
psoriasis has higher numbers of Malassezia spp. and Streptococcus spp. and lower numbers of
Cutibacterium spp. compared to healthy individuals.117
The crosstalk between commensals and the skin may involve microbial metabolite-mediated
interactions with cells in the immune system. Mucosal-associated invariant T (MAIT) cells
constitute a subset of αβT lymphocytes characterized by a semi-invariant T cell receptor
alpha (TCRα) chain. MAIT cells have innate, T cell effector-like qualities.118,119 Microbial
exposure that occurs during early life imprints MAIT cell abundance for life. MAIT cells
represent a dominant type-17 effector subset in the skin, they are involved with immune
surveillance, and they defend against microbial infection. MAIT cells require vitamin B2
metabolites that are only produced by bacteria and fungi.86 The major histocompatibility
complex (MHC) class I-like protein, MR1, is responsible for presenting bacterially-produced
riboflavin (vitamin B2) and folic acid (vitamin B9) metabolites to MAIT cells.118,120-122 After
the presentation of foreign antigen by MR1, MAIT cells produce the proinflammatory
cytokines, interferon-γ (IFN-γ) and tumor necrosis factor, and they are cytolytic.118
Most species within the dominant bacterial taxa Corynebacteriaceae, Propionibacteriaceae,
and Staphylococcaceae in the skin microbiome encode Vitamin B2 biosynthesis therefore,
MAIT cell specific immunity through recognition of riboflavin biosynthesis intermediates
produced by the skin microflora is an example of crosstalk between commensals and the
skin that plays an important role in skin barrier immunology.123-127

507 Evolution and Challenges of Sustainability
The crosstalk between commensals and the skin may also depend on the effects of host-derived
molecules on the skin microbiome. Kang et al. demonstrated that oral supplementation
of human subjects with vitamin B12 (i.e., cobalamin), which is an essential co-factor for
humans, resulted in a transcriptional and metabolic shift in C. acnes that involved down-
regulation of genes involved in vitamin B12 biosynthesis and differential expression of
genes with both known and unknown association to vitamin B12 metabolism.128 Vitamin
B12 supplementation to test subjects also promoted the production of porphyrin by C.
acnes. Prophyrins are proinflammatory and are implicated in acne pathogenesis.129,130 This
demonstrated that host-acquired micronutrients are accessible to the cutaneous microflora
and that back-and-forth crosstalk between the host and the skin microbiome may play
important roles in disease development. Although vitamin B12 is essential to human
health, this work suggests that avoiding excessive amounts in the diet may reduce porphyrin
production by C. acnes, which in turn should decrease inflammation and the severity of acne.
THE SKIN ENVIRONMENT FOR MICROORGANISMS
The skin provides a living environment for resident microorganisms. The structure of skin
and the nutrients on skin for microorganisms depend on factors including an individual’s
age, sex, health status, hygiene practices, lifestyle, and environmental exposure. The outer
layer of the epidermis continually sheds keratinized skin cells with complete turnover
about every 28 days, and it has been estimated that about 10% of exfoliated cells contain
bacteria.69,106 A large proportion of the skin microbiome consists of resident microorganisms
that generally are stable, but there is a smaller percentage of transient microorganisms
that can opportunistically colonize niches when the skin is compromised.131 The skin
microflora at different sites on the body are those that are best able to take advantage of
the physical and chemical environments in various niches using substrates in sweat, sebum,
and exfoliated cells along with varying levels of exposure to ultraviolet radiation, moisture,
oxygen availability, and pH.106
The skin surface pH is reported to be around pH 5.6 66 however, the skin surface pH
of healthy individuals may range from around pH 3.5 to over pH 7, depending on the
individual and the anatomical site tested.132 Eccrine glands are primarily responsible for
excretion of water and electrolytes, but may also include minor amounts of glucose, pyruvate,
lactate, cytokines, immunoglobulins, and AMPs.133,134 The low pH and dry environment
(i.e., low water availability) at relatively dry skin sites (e.g., volar forearm) restrict growth
of many microorganisms, such as the Proteobacteria that are not acid and low a
w tolerant.
More moist/higher pH regions such as the navel, axillary, umbilical, and inguinal regions
allow growth of a greater diversity of microorganisms that are able to utilize the available
substrates for growth.
CHANGES IN THE SKIN MICROBIOME WITH AGE
Until recently, it was believed that microorganisms colonize the infant’s skin at the time
of birth. However, studies now show that colonization occurs in the mother’s body and
that the uterine cavity, placenta, and amniotic fluid may not be sterile.135,136 The placental
microbiome consists mainly of commensal microorganisms from Firmicutes, Tenericutes,
Proteobacteria, Bacteroidetes, and Fusobacteria phyla.66 Tenericutes (now renamed to