EFFECT OF NATURAL ANTIMICROBIALS ON THE SKIN MICROBIOME 79 There has been signifi cant research investigating a second bacterium commonly found on the skin, Corynebacterium jeikeium. This microbe offers epidermal protection via a mutualistic relationship with the host. It is a ubiquitous and primarily innocuous bacterium that recently has been found to use manganese acquisition to protect from superoxide radicals (3). This is important for cosmetic chemists, as the enzyme superoxide dismutase may also function to prevent oxidative damage in epidermal tissue. Because C. jeikeium scav- enges iron and manganese, researchers propose it may also serve as a way to prevent colo- nization by other invaders. Given the prevalence of skin colonization, the relative rarity of C. jeikeium pathogenesis and the unexplored benefi ts of the bacterium indicate that this microbe probably lives mutually with other microbes and epithelial cells and has more positive than negative effects on the skin (3). By isolating cultures of Corynebacterium, it is also assumed that they could be used to prevent or control oxidative damage to the skin. In addition, the Cory- nebacterium glutamicum strain (a Corynebacterium with functional capabilities) has the capac- ity to produce glutamic acid. The production of a compound and the way in which it interacts with the skin could have a potential effect on downstream targets that cosmetic chemists focus on, such as moisturization. Propionibacterium acnes is often associated with the detrimental effects of acne, as it is well established that both healthy and acne-prone patients are colonized with the bacterium. Acne may be triggered by many intrinsic and extrinsic factors as comprehensive research on the ailment has demonstrated. However, P. acnes involvement in infl ammation is a relatively minor one. It is proposed that the abnormal growth of this organism, which is often associated with acne blemishes and pustules, might be a side effect of infl ammation, rather than the root cause of it (3). Studies have shown that antibiotics have mostly reduced infl ammation in said volunteers affected with acne, whereas only secondarily inhibiting P. acnes growth. Because P. acnes is present on healthy skin and acne-prone skin alike, the authors suggest that it may serve more as a mutualistic microbe than a pathogenic one (3). These data taken in conjunction with the aforementioned studies suggest that along with the other microbes commonly associated with infection or disease, these may actually have a lower pathogenic potential than initially hypothesized, with minor roles in the true development of the signs and symptoms associated with acne. Furthermore, researchers have also used mice, immunized with heat-killed P. acnes, and subsequently challenged them with lipopolysaccharides. The results showed that these mice had increased TLR4 sensitivity and lymphocyte antigen 96 (MD 2) up- regulation, which means that the increased cytokine levels was a direct indication of the detrimental effects of P. acnes in vivo (3). This suggests that P. acnes has the ability to enable host cells to respond effectively to pathogenic trauma. Cogen et al. pro- posed that because of this, it is probable that a similar response could be observed if injections of other types of bacteria were used, serving to highlight another potential mechanism. It is theorized that the supply of nutrients found in the ecological envi- ronment of P. acnes, such as sebum, is a direct exchange for protection against other pathogenic microbes P. acnes defends against (3). Streptococcus and Pseudomonas, microbes highly present in the human microbiome, have been studied in terms of their detrimental contributions to infection and disease. How- ever, Cogen et al. now suggest that they may also serve the host in a protective role,
JOURNAL OF COSMETIC SCIENCE 80 specifi cally in regard to epithelium interactions. Streptococcus pyogenes secretes pore-forming toxins, such as streptolysin O, which are found to promote wound healing in vitro via stimulation of keratinocyte migration. Research suggests that sublytic concentrations of this toxin may induce CD44 expression, potentially modulating collagen, hyaluronate, and other extracellular matrix components in the skin (3). These fi ndings were investigated in mouse models, but support the possibility that Streptococcus and some of its metabolites have the potential to be used as a type of probiotic for the skin. Both the tight skin mouse model of scleroderma and other models mimicking fi brosis showed decreased levels of hydroxyproline after treatment with that toxin. Results indicated that activation in the epidermis leads to a poten- tial reepithelialization of wounds in keratinocytes. Streptokinase is also being con- sidered for clinical use in therapeutic fi brinolysis, according to the British Journal of Dermatology (3). Although these toxins secreted by this bacterium may be harmful in large doses, in a tissue-specifi c context, researchers implore that limited expression of S. pyogenes factors may help rather than harm the host. The protective role of Pseudo- monas, or Pseudomonas aeruginosa specifi cally, should also be considered despite re- search supporting its initially intermediate involvement in disease. There are some commercial medications on the market today that use by-products of these microbes, such as pseudomonic acid A (mupirocin). Mupirocin is a topical antibiotic developed from Pseudomonas fl uorescens to treat infections caused by other pathogenic microbes (3). The development of this antibiotic again not only supports the protective role of this fl ora but also allows us to transition into the possibility of using such microbes and their by-products to promote healthy skin. A peptide produced by P. aeruginosa was also found to have potent antibacterial activity against pathogenic invaders, in a similar light to the Lactobacilli organisms described previously. This along with other investigative studies alluding to the protective role of P. aeruginosa suggests that commensals such as Pseudomonas maintain homeostasis, rather than causing it. Cogen et al. summarized the importance of this well: the ubiquitous presence of these and other commensals may be necessary to not only promote protection from other invad- ing microbes via competitive inhibition and excretory techniques, but they may also serve effi cacious roles by promoting overall skin health. The protective antimicrobial capabilities of Lactobacilli have been thoroughly inves- tigated, as the primary function of these lactic acid–producing fl orae is to protect the host by limiting the growth of other pathogens. These fl orae are commonly used in food-grade digestive probiotics and protect the gastrointestinal tract. In cosmetics, short-chain peptides derived from the fermentation of this organism may be used in personal care applications. Antimicrobial peptides are relatively short, protein-like compounds that are typically 30–60 amino acids in length (4). These peptides are a type of aforementioned bacteriocin, typically produced by bacteria as a defense mechanism to outcompete other microorganisms that may reside in the same topo- graphic environment on the body. In addition to Lactobacilli, the class of lactic acid bacterium can be expanded to include microorganisms such as Enterococcus, Pediococ- cus, and Leuconostoc. These microbes serve as a type of protective armor for the skin to help combat disease. Prince et al. investigated the role of Lactobacilli in protecting the host from infection and found that Lactobacilli reuteri specifi cally protects kerati- nocytes by competitive exclusion of the invading pathogen from its binding sites on the cells (5).
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