Patrick L.J.M. Zeeuwen; Michiel Kleerebezem; Harro M. Timmerman; Joost Schalkwijk


Curr Opin Allergy Clin Immunol. 2013;13(5):514-520. 

In This Article

Microbiota and Skin Diseases

The 'hygiene hypothesis', which was adduced in 1989 for the first time, postulated that declining family size, improvements in household facilities, and higher standards of personal cleanliness has resulted in more widespread clinical expression of atopic diseases.[25] It is nowadays more and more accepted that the recent increase in allergic and (chronic) inflammatory diseases is a result of our modern western lifestyle, and that this is also associated with changes in the human microbiome.[26] Furthermore, the recently proposed 'biodiversity hypothesis' implies that limited exposure to various environmental microbiota leads to aberrant development of our immune system,[27] and that environmental biodiversity is linked to microbiota diversity and human health. It was shown that atopic individuals, compared with healthy controls, have lower skin microbiota diversity of Gammaproteobacteria, which correlated with lower environmental biodiversity in the surroundings of their homes.[10] The disturbance of homeostatic relations between the host and its microbiota might also be a driving factor in inflammatory skin diseases such as atopic dermatitis and psoriasis[28] (Fig. 1). Recently, it was reported that mutations in the epidermal expressed filaggrin (FLG) gene are associated with atopic dermatitis and other allergic diseases,[29,30] and that copy number variation of epidermis-expressed genes such as β-defensins and LCE3B/C predispose to psoriasis.[31,32] These observations strongly suggest that variation of the skin barrier and consequent cutaneous sensitization by penetration of microbes or pathogen-associated molecular patterns plays an important role in these two most common inflammatory skin diseases. To understand the role of microbes in inflammatory and allergic skin diseases, a few groups have recently analysed the skin microbiome of diseased and injured skin.

Figure 1.

Model for homeostasis and dysbiosis in normal skin and atopic dermatitis skin. The microbiota composition of normal healthy skin consists largely of bacteria that belong to Firmicutes (mainly Staphylococcus spp. like Staphylococcus epidermidis, depicted in yellow) and Actinobacteria (Propionibacterium and Corynebacterium, depicted in blue). In atopic dermatitis, the skin is often colonized by Staphylococcus aureus (depicted in red), whereas the abundance of other bacteria is decreased. See also Supplemental Table 2, for more specific microbe–microbe or host–microbe interactions related to skin immune function and skin barrier function. AMP, antimicrobial protein; PAMP, pathogen-associated molecular pattern.

The presence of Staphylococcus aureus, which is found on the skin in more than 90% of atopic dermatitis patients, is thought to play an important role in the pathogenesis of this disease,[33] as some treatments to reduce S. aureus colonization proved to decrease severity of atopic dermatitis.[34] However, it is unlikely that a single species causes atopic dermatitis. In a recent study,[35] the microbiota composition of lesional skin of moderate-to-severe paediatric atopic dermatitis patients was analysed at baseline, during disease flare, and posttreatment, revealing that temporal shifts in skin microbiota composition were associated with disease flares and treatment. More specifically, the relative abundance of S. aureus and, surprisingly, also the skin commensal Staphylococcus epidermidis was increased with clinical disease activity, whereas species of the genera Streptococcus, Propionibacterium, and Corynebacterium were increased following therapy. One could speculate that the increased abundance of S. epidermidis in lesional atopic dermatitis skin reflects a microbial response to overgrowth of S. aureus, as S. epidermidis is able to selectively inhibit S. aureus[13]. Overall, the atopic dermatitis skin of the inner elbow and the back of the knee, two areas that are commonly affected in atopic dermatitis patients, showed a much lower microbiota diversity relative to the same skin area of healthy controls[35] (Supplemental Table 1, This suggests that the changing milieu of lesional atopic dermatitis skin might be a perfect microenvironment and substrate for specific (staphylococcal) species.

The pathogenesis of psoriasis has also been associated with changes in the skin microbiota.[36] The first microbiota study[37] in patients with psoriasis revealed that the bacterial composition of the lesional skin was much more diverse than that observed in skin from healthy individuals or nonlesional skin from psoriatic patients. Firmicutes was the most abundant and diverse phylum populating the psoriatic lesions, whereas the genus Propionibacterium was significantly underrepresented compared with nonlesional skin samples from psoriasis patients, or healthy controls. However, these results appear to be contradicted by a subsequent study[38] that analysed the skin microbiota of whole skin biopsies. It was shown that the microbiota diversity in psoriatic lesions was reduced relative to normal skin. In addition, also the genera that were present at discriminating abundance levels were different. These apparent contradictions may be because of different sampling techniques, wherein the first study determines the microbiota composition using swab samples, whereas the subsequent study analysed the microbiota from the complete epidermis and dermis. As recent studies[23,24] have shown that bacteria are also present in deeper parts of the skin, one could imagine that the microbiota of the superficial layer is just a part of the total host indigenous skin microbiota. However, it remains unclear whether disease-associated changes in the microbiota composition have a causal role in disease development or are merely the result of abnormal skin biology, which may depend primarily on host-specific genetic determinants and skin immune-system variation that are highly prevalent in inflammatory skin diseases like atopic dermatitis and psoriasis.[29–32,39,40]