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The Microbiome Movement: Commensal Cosmetics Offer a Viable Future

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The human skin serves as a barrier to the outside world and is rich in microorganisms, which play a crucial role in maintaining human health.17 The skin microbiome—much of which is initially acquired at birth8—is comprised of diverse communities of microorganisms that populate the skin, and a square centimeter of skin can contain up to a billion microorganisms (see Figure 1).9 These diverse communities of bacteria, fungi, mites and viruses can provide protection against disease and form dynamic yet distinct niches on the skin.10 Bacteria are often considered the most abundant microorganisms in the skin ecosystem, and reside from within the top layers in the skin down to the dermal layer.

The skin microbiome is highly diverse and there is a significant degree of intra-individual variation as well as inter-individual variation. Within an individual, various microenvironments based on temperature, moisture, pH, sebum content, UV light exposure, etc., give rise to varying populations of microbes.6 Based on these conditions, the skin microbiome can essentially be categorized by skin type: sebaceous (e.g., the forehead and back); moist (e.g., the nares, inguinal crease, umbilicus, toes and armpit); or dry (e.g., the forearm, palm or buttocks).6 The dry regions tend to be dominated more by proteobacteria, while the moist areas tend to be dominated by firmicutes, particularly by staphylococcaceae.6 The sebaceous regions are dominated by actinobacteria—for example, corynebacteriaceae or propionibacteriacea. In general, the sebaceous regions of skin are typically less diverse compared to dry or moist skin types.

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Between individuals, there is also a high degree of variability. In a study of the hand microbiome, hands from the same individual shared only 17% of species-level identity, whereas hands from different individuals shared only 13%.11 There is also a higher correlation of the microbiome between related individuals or individuals in the same household. Characteristics that contribute to interindividual variability include host factors (e.g., ethnicity,12 age13 or sex14, 15), environmental factors (e.g., humidity,16 temperature,16 or UV light exposure17), or behavioral factors (e.g., cosmetic18 or soap use,11 etc.). These factors shape an individual’s skin microbiome, which has key effects on skin appearance and health.

The Microbiome and Skin

A stable microbiome is essential to maintaining skin health since microorganisms closely interact with the skin’s biology and skin barrier, and vice versa.19 Examples of this symbiotic relationship between microbes and the human skin include cross-talk with the cutaneous immune system,20 stimulation of antimicrobial peptide secretion and protection against pathogenic bacteria21 and stimulation of ceramide production—all of which provide beneficial effects to the skin.

As an example, S. epidermidis, a non-pathogenic skin commensal, has been characterized to exhibit a number of these properties. For instance, S. epidermidis secretes lipoteichoic acid, which binds to Toll-like receptor 2 (TLR2) to inhibit inflammatory responses and thereby limit tissue damage and promote wound healing.22 Moreover, Naik et al. found that S. epidermidis applied to the skin of germ-free mice resulted in the specific development of protection against cutaneous pathogens.23 S. epidermidis also synthesizes Esp, which degrades proteins that are crucial for S. aureus biofilm formation and host epithelial adhesion.24

Interestingly—and contrary to popular belief—a higher degree of diversity in the skin microbiome is associated with healthier individuals. Low microbial diversity has been characterized in patients with damaged skin, compared with healthy individuals.25, 26 In fact, on a larger scale, western cultures are reported to have a much lower degree of microbial diversity compared with rural populations or more remote populations.18 This is most likely related to the higher use of antibiotics in western and urban populations, and the result (or at least strong association) is the concurrent rise in skin allergies and other skin problems.27 Meanwhile, studies from remote populations—for example, in South America—have revealed microbiomes of enormous microbial diversity,28 suggesting a loss of microbial diversity in western and urban peoples over time.

Disruptions in the Skin Microbiome

A common oversimplification of the skin microbiome is the binary classification of individual microbes as either beneficial or harmful. In reality, skin microbes are much more complex and can act in either a beneficial or harmful manner under different scenarios; for example, in compromised or healthy skin. In other cases, the ecological dynamics of bacteria interacting in a system add complexities to their characteristics. For example, one particular microbe may be benign while on its own but may increase in its relative abundance to other microbes on the skin and cause a cutaneous response.

However, increasing evidence has associated altered microbial communities, or dysbiosis in the skin, with unhealthy skin,9, 29—especially eczema,30, 31 which is greatly associated with higher populations of Staphylococcus aureus. In addition, several studies have found disruptions in the skin microbiome in compromised skin, observing a lower microbial diversity in it than in healthy skin.18 The same is true for chronic wounds.26, 32 Mechanistically, when a skin lesion occurs, a local cascade of inflammatory signals, e.g., cytokines, is released in response to microbes that enter the site of injury. Such changes in the local cutaneous immunity drive signals that interact with skin microbes.

A stable microbiome is essential to maintaining skin health since it interacts with the skin's biology and barrier, and vice versa.

In the case of higher body odor—which is, to a large extent, caused by the metabolism of sweat and sebaceous excretions by the skin microbiota—associations have been made with certain species. These connections are largely tied to the ability to metabolize dipeptide-conjugated thioalcohols such as S-[1-(2-hydroxyethyl)-1-methylbutyl]- (L)-cysteinylglycine. S. hominis, S. haemolyticus and S. lugdunensis, in particular, can metabolize these compounds and are therefore more highly associated with body odor. In contrast, S. epidermidis and Corynebacterium tuberculostearicum show little metabolic ability of these types of compounds and, while present in high numbers in the armpit, are typically not associated with body odor.33

Dandruff, characterized by mild seborrheic dermatitis, has been weakly associated with skin microbiome disruptions, particularly Malassezia restricta and Filobasidium floriforme. Additionally, recent studies have revealed significant changes in the microbiome due to aging. In general, the microbial diversity of the skin increases with age, but a closer analysis has revealed increases in specific microbial species over time, some of which have been associated with skin conditions.34

As another example, the presence of specific strains of Propionibacterium acnes (P. acnes) has been highly associated with subjects presenting with acne.35 Studies also have found an increased presence of the skin mite Demodex folliculorum in patients with rosacea,36 as well as general dysbiosis in psoriasis.37

However, the key issue that remains to be elucidated is the causality of these observations—in other words, is the observed dysbiosis the cause or effect of abnormal skin? There is no clear answer, but in many cases, the dysbiosis and abnormal skin occur synchronously.

Cosmetics and the Skin Microbiome

The use of topical cosmetics, soaps and toiletries on the skin may have a profound impact on the microbiome, and these effects are only beginning to be elucidated. The use of antibiotics, handwashing or lotions, for example, may alter the microbial community and create an opportunity for skin pathogens to colonize the skin;38 of course, handwashing is still necessary and highly recommended.

In one study in mice from the University of Pennsylvania, the topical antibiotics bacitracin, neomycin and polymxin were shown to create drastic shifts in the skin microbiome, compared with the antiseptic treatments ethanol or iodide. Furthermore, the antibiotic-treated mice were more susceptible to S. aureus infection, which is potentially pathogenic.39 The judicious use of topical antibiotics is therefore an important consideration. S. aureus also can have a number of deleterious effects on the skin since it can produce virulence factors, lysins and proteases, and disrupt the epidermal barrier.40, 41

As another example, occluding skin abrasions with bandages or other barriers may promote an overgrowth of potentially pathogenic anaerobes—S. aureus, for example.42, 43 In yet another study, topical cosmetic use was associated with a higher Propionibacterium concentration, but the results varied by skin hydration levels in the study subjects.44

While not all cosmetics negatively affect the skin microbiome, the potential impact of topical agents on the microbiome must be considered during product development, as disruptions in the microbiome clearly impact skin health. Most notable are the effects of antibiotics that can create opportunities for the entry of S. aureus, which could be problematic. A summary of these complex interactions between cosmetics, skin microbes and skin characteristics is presented in Figure 2.

Topical Product Considerations

Topical prebiotics: One microbiome-based strategy in topical products is the use of prebiotics. This is a broad term that refers to the application of an ingredient that selectively allows for the growth of desirable microorganisms.45 In the context of the gut microbiome, this may include fiber or a type of polysaccharide. In the skin, prebiotics typically involve the inclusion of certain carbohydrates—for example, fructo-oligosaccharides. However, there is little evidence on the efficacy of prebiotics in the context of the skin microbiome.

Topical probiotics and live bacteria: A growing strategy in skin care is to use certain strains of actual live bacteria topically. These are sometimes known as probiotics. For example, Lactobacillis is commonly explored for topical use and is classified by the U.S. Food and Drug Administration (FDA) as Generally Regarded as Safe (GRAS).46 Other approaches have invoked the topical use of ammonia-oxidizing bacteria for the treatment of a number of skin disorders, while others are using beneficial strains of P. acnes to treat acne.

As another example, early studies have shown that topical application of different strains of wild-type S. epidermidis may be a viable therapeutic approach to treating skin diseases. In a double-blind, randomized clinical trial in Japan, for example, topical application of autologous S. epidermidis in healthy volunteers increased lipid content of the skin, suppressed water evaporation and improved skin moisture retention. It also promoted acidification of the skin surface—all without significant undesirable effects.47

Not only does topical application of S. epidermidis appear to have beneficial structural and compositional effects, but also positive cutaneous immuno-modulatory effects. The topical application of certain strains of S. epidermidis has demonstrated that it may enhance innate skin immunity and limit pathogen invasion.21

In a further study by Gallo’s group, species of S. epidermidis and S. hominis were isolated and demonstrated activity against S. aureus. Topical application of these strains to human subjects with eczema also reduced S. aureus colonization.48 The topical application of S. epidermidis, S. hominis and other “beneficial” or benign skin commensals represents a significant opportunity in the cosmetic market for potentially reducing infections, and improving skin hydration, moisture and pH. While few well-characterized, topically applied live bacteria are on the market, many are in development and advances are being made in their technical characterization and feasibility.

Topical S. epidermidis appears to have beneficial structural, compositional and immuno-modulatory effects.

Manufacturing and translational considerations: Some additional key considerations for the topical application of live bacteria in cosmetics are necessary for their eventual widespread use. For example, the scale-up and manufacturing of live bacteria is complex and requires large-scale fermentation capacity in a highly controlled environment. Formulation of these bacteria—whether they are freeze-dried or used live without any additional preparation—is also complex, as the manufacturing of the bacteria determines whether the formulation is aqueous or non-aqueous, or whether a two-step formulation is required. Additionally, the excipients used in the formulation must not be harmful for the bacteria. All of these challenges are surmountable, as companies have begun to scale up the production of bacteria used in cosmetics; however, the challenges of using living organisms in cosmetics are quite distinct from traditional challenges faced by the industry.

Summary and Future Directions

While it is clear the microbiome plays a certain role in skin health, it remains a highly complex entity due to its high level of variability within and between individuals—and the exact relationship between the cause and effect of dysbiosis and abnormal skin conditions remains to be elucidated. Nevertheless, the potential for harnessing the skin microbiome for cosmetics and skin care remains enormous, especially as new approaches emerge for the use of live bacteria in cosmetics and for evaluating the impact of cosmetics on the microbiome. The frontier, while challenging, is wide open for innovation in the cosmetics industry.

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