Skin Barrier Insights: From Bricks and Mortar to Molecules and Microbes
January 2019 | Volume 18 | Issue 1 | Supplement | s63 | Copyright © 2019
Carol A. Bosko PhD
Unilever Research & Development, Trumbull, CT
for antimicrobial defense, enzyme activity, and cytokine activation. Elevated SC pH is associated with perturbations in barrier function as many enzymes involved in lipid metabolism and CD degradation require an acidic environment.44 Elevated pH is also associated with shifts in the microbial composition toward potentially pathogenic organisms.45 These findings provide support for use of acid-neutral pH cleansers and moisturizers in the prevention and treatment of barrier deficiencies.46 Microbiome The skin harbors a diverse population of microbes whose composition is largely determined by site-specific factors such as moisture and sebum content.47 The skin’s invaginations and appendages harbor a large number of microorganisms but microbial DNA has also been found deep within the dermis.48 This surprising finding challenges many existing concepts of skin, its microflora, and the mechanisms by which the host immune system is educated by the microbiome.The SC provides a formidable barrier to microbial colonization due to the physical barrier, low water and nutrient content, acidic pH, and antimicrobial lipids (AML) and peptides (AMP). Sphingosine and free fatty acids are potent AMLs and are found in ample concentrations in SC.49 AMPs are a diverse, yet highly conversed set of proteins belonging to the host innate immune system that kill microbes primarily through disruption of the cell membrane. The predominant AMPs of skin belong to the cathecidin and defensin classes and are delivered to the SC via LGs or glandular secretions.50 However, microbes can also produce AMP-like proteins. S. epidermidis produces AMPs that inhibit colonization of S. aureus,51 however strain variation is significant, and the commensals in some AD patients lack the ability to produce AMPs selective for S. aureus.52 Microbial AMPs also synergize with host AMPs, thus the secretome of commensals could be viewed as an integral part of most innate defense system.53 There exists a complex interplay between the microbiome and the host immune system. The innate and adaptive arms of the immune system modulate the composition of the microbiome and in turn, the microflora communicates with and directs the host immune response.54 Propionibacteria acnes induces expression of AMPs and inflammatory cytokines in keratinocytes in a toll-like receptor-dependent (TLR) fashion.55 Staphylococcal lipoteichoic acid blunts inflammation via interaction with TLR3 and stimulates wound healing.56 These are but a few examples that illustrate how the microflora directly modulates both the innate and adaptive arms of the host immune response. The complexity of this interaction suggests a coevolution of host and microbes and this balance may be disrupted by our rapidly changing environment; diet, hygiene, and antibiotics could affect the microbiome at a faster rate than the microbiota can adapt. This has led some researchers to speculate that these changes are responsible for the dramatic increase in the incidence of inflammatory diseases such as AD.Barrier perturbations can drive changes in the skin’s microbiota, ie, dysbiosis. There is now a strong recognition that barrier dysfunction is a driving element in many inflammatory skin disorders and not merely a bothersome sequela. Most notably patients with AD tend to be at increased risk of infection and colonization by S. aureus.57 In contrast to the many microbiome studies on AD patients, definitive studies on microbial changes that might accompany cosmetic dry skin are yet to be published.58 On the other hand, mild cleansers have been shown to help restore normal flora.59 The use of mild cleansers that protect the skin’s barrier lipids60,61 would be expected to help maintain a “healthy” microbiome.
Barrier impairment, whether the result of genetic or environmental influences, increases the flux of water out of and exogenous materials in to the skin. The consequences of this increased permeation will depend, in large part, on the host response to that stimulus. In some instances, the host response can further degrade barrier function leading to a vicious cycle of stimulus and response. Optimizing a skin care regime to support the skin’s own barrier repair mechanisms is an integral part of any successful therapy. Continued research efforts are necessary to provide the scientific foundation for identifying new therapies and optimal skin care regimes.
Carol Bosko is an employee of Unilever.
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Carol A. Bosko PhD