The purpose of the present manuscript is to review the chemical and physical properties of epidermal...

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity—the sphingoid basesd-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid—against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P< 0.0001) for each bacterial species exceptSerratia marcescensandPseudomonas aeruginosa.d-Sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria exceptS. marcescensandP. aeruginosa(MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active againstStreptococcus sanguinis,Streptococcus mitis, andFusobacterium nucleatumbut not active againstEscherichia coli,Staphylococcus aureus,S. marcescens,P. aeruginosa,Corynebacterium bovis,Corynebacterium striatum, andCorynebacterium jeikeium(MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria exceptE. coli,S. marcescens, andP. aeruginosa(MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.

The skin is the largest organ of the body and consists of an epidermis, dermis and subcutaneous adipose tissue. The skin surface area is often stated to be about 1.8 to 2 m² and represents our interface with the environment; however, when one considers that microorganisms live in the hair follicles and can enter sweat ducts, the area that interacts with this aspect of the environment becomes about 25–30 m². Although all layers of the skin, including the adipose tissue, participate in antimicrobial defense, this review will focus mainly on the role of the antimicrobial factors in the epidermis and at the skin surface. The outermost layer of the epidermis, the stratum corneum, is physically tough and chemically inert which protects against numerous environmental stresses. It provides a permeability barrier which is attributable to lipids in the intercellular spaces between the corneocytes. In addition to the permeability barrier, there is an innate antimicrobial barrier at the skin surface which involves antimicrobial lipids, peptides and proteins. The skin surface has a low surface pH and is poor in certain nutrients, which limits the range of microorganisms that can survive there. Melanin and trans-urocanic acid provide protection from UV radiation, and Langerhans cells in the epidermis are poised to monitor the local environment and to trigger an immune response as needed. Each of these protective barriers will be discussed.

The primary purpose of the epidermis of terrestrial vertebrates is to produce the stratum corneum, which serves as the interface between the organism and the environment. As such, the stratum corneum provides a permeability barrier which both limits water loss through the skin and provides a relatively tough permeability barrier. This provides for a degree of resistance to mechanical trauma and prevents or limits penetration of potentially harmful substances from the environment. The stratum corneum consists of an array of keratinized cells embedded in a lipid matrix. It is this intercellular lipid that determines the permeability of the stratum corneum. The main lipids here are ceramides, cholesterol, and fatty acids. In addition, the skin surface of mammals, including humans, is coated by a lipid film produced by sebaceous glands in the dermis and secreted through the follicles. Human sebum consists mainly of squalene, wax monoesters, and triglycerides with small proportions of cholesterol and cholesterol esters. As sebum passes through the follicles, some of the triglycerides are hydrolyzed by bacteria to liberate free fatty acids. Likewise, near the skin surface, where water becomes available, some of the ceramides are acted upon by an epithelial ceramidase to liberate sphingosine, dihydrosphingosine, and 6-hydroxysphingosine. Some of the free fatty acids, specifically lauric acid and sapienic acid, have been shown to have antibacterial, antifungal, and antiviral activity. Also, the long-chain bases have broad spectrum antibacterial activity.

PubMed searches reveal much literature regarding lipids in barrier function of skin and less literature on lipids in barrier function of the oral mucosa. In terrestrial mammals, birds, and reptiles, the skin’s permeability barrier is provided by ceramides, fatty acids, and cholesterol in the outermost layers of the epidermis, the stratum corneum. This layer consists of about 10–20 layers of cornified cells embedded in a lipid matrix. It effectively prevents loss of water and electrolytes from the underlying tissue, and it limits the penetration of potentially harmful substances from the environment. In the oral cavity, the regions of the gingiva and hard palate are covered by keratinized epithelia that much resemble the epidermis. The oral stratum corneum contains a lipid mixture similar to that in the epidermal stratum corneum but in lower amounts and is accordingly more permeable. The superficial regions of the nonkeratinized oral epithelia also provide a permeability barrier. These epithelial regions do contain ceramides, cholesterol, and free fatty acids, which may underlie barrier function. The oral epithelial permeability barriers primarily protect the underlying tissue by preventing the penetration of potentially toxic substances, including microbial products. Transdermal drug delivery, buccal absorption, and lipid-related disease are discussed.