The gut and its bacterial flora – its ‘microbiome’ – is receiving a lot of attention from scientists and their findings are being closely followed by the lay press. The skin’s microbiome, too, has become a hot topic among dermatologic researchers, as evidenced by the number of papers and reports dealing with the subject at the 2013 International Investigative Dermatology meeting in Edinburgh. Of these reports, several dealt with the microbiome in atopic dermatitis (or eczema). This is of particular importance to clinical dermatology because infections with Staph. aureus is a common trigger of disease flares among atopics.
Dr. Julie Segre’s laboratory at the National Institutes of Health has pioneering the work on the complexity of the human skin microbiome. She presented an overview of the microbiome on normal and atopic skin. While there is substantial variation from individual to individual in the prevalence of bacterial species and classes on normal skin, these person to person differences are less marked than the regional differences within an individual. Some bacteria flourish in moist areas, like arm pits, while others predominate on oilier facial skin, and still others prefer a dry arm or leg. Many of the bacteria her group has identified in our skin flora were not known to inhabit the skin prior to her studies. This is because earlier work relied upon in vitro culture systems, while her studies are based upon identification of microbial DNA in skin swabs. Clearly, many of the predominant species of normal skin flora do not flourish on agar! Yet, her pioneering work has also confirmed the over-representation of pathogenic strains of Staphylococcus in skin swabs from all sites in people with atopic dermatitis. Overload with Staphylococcus aureus on atopic skin and its frequent role in disease flares has been recognized for decades, but the reasons for this are only beginning to be understood.
In recent years, the basis for S. aureus overgrowth in atopic skin has been attributed to the overproduction of cytokines derived from Th-2 lymphocytes. One of these ‘bad actors’, the cytokine IL-4, decreases the production of two important epidermal antimicrobial peptides, human beta-defensin 2 and the cathelicidin peptide, LL-37 – which both are needed to ward off bad bacteria. But now, it appears that the antimicrobial defenses of the skin are complex, and several different abnormalities may be interacting to produce the propensity for staph infections in atopics.
In a talk on the antimicrobial peptides of skin, Dr. Jens Schroeder from the University of Kiel, Germany, discussed an important role of the normal flora through their own production of peptides that inhibit the growth of pathogenic bacteria, like Staph. He also reported his intriguing observation of remarkable similarities between the amino acid composition of portions of some corneocyte proteins, such as filaggrin, and some of these antimicrobial peptides produced by the normal flora. He proposed that when filaggrin is degraded in the stratum corneum into smaller units, these bacteria may utilize some of these fragments to synthesize their antimicrobial peptides. If this proves to be true, it would constitute a remarkable example of consensual evolution, with the skin providing its favored resident bacteria with the building blocks that they need to generate antimicrobial molecules that protect the skin from disease-causing bacteria, and at the same time ensure the good bacteria of a foothold on their favored soil.
Schroeder’s hypothesis could also provide another mechanism underlying the prevalence of Staph. aureus. Atopics have a deficiency of filaggrin – as a result of one of several common genetic mutations, particularly prevalent among northern Europeans, and/or because the ‘bad’ Th2-derived cytokines also decrease filaggrin synthesis. This filaggrin deficiency could set up the skin of people with atopic dermatitis for weakened antimicrobial defenses against the ‘bad bugs.’ Unable to feed the good, normal skin flora the precursor protein pieces they need to generate their own territory-defending antimicrobial peptides, atopic skin would then be a sitting duck for pathogenic staph in the environment. While this story is still in an early phase of discovery, the concept is most intriguing.
Dr. Richard Gallo and his colleagues at the University of San Diego reported other features of the relationship between the normal flora and colonizing pathogens. Previously, they determined that certain members of the normal flora stimulate the production of the antimicrobial peptide, LL-37. Now, they show that one previously overlooked member of the normal flora, Staphylococcus hominis, produces at least two new antimicrobial peptides that exhibit strong activity against S. aureus. This mechanism likely contributes to the ability of the normal flora to fend off potential invaders. But as S. aureus begins to replace S. hominis on atopic skin, production of these two helpful proteins almost certainly would cease. This may be what tips the balance in some patients from colonization by S. aureus to overt skin infection and the concomitant disease flares.
Bottom Line: Together, these studies now provide several mechanisms (in addition to a defective skin barrier itself, which is undoubtedly contributes to impaired antimicrobial defense) that help to explain the unfortunate tendency for atopic dermatitis skin to be readily colonized, and not infrequently invaded by S. aureus.