**2.2.1 Bacteria**

Coagulase-negative *Staphylococcus* species are Gram-positive cocci. This group comprises *Staphylococcus* species other than *Staphylococcus aureus* and includes more than 10 species as *Staphylococcus epidermidis*. These bacteria grow under the aerobic condition and live in the colonisable layers of the skin. The term 'colonisable layers' here includes stratum corneum, the outermost barrier layer of the epidermis, and the outer thin section of viable layers of epidermis underneath the stratum corneum. These species can also grow under strict anaerobic conditions. This allows them to grow not only on the very surface of the skin but also deeper within skin layers where they compete for oxygen with other species. They are known to form grape-like clumps when cultured and normally also exist as clumps in skin layers.

*Propionibacterium acnes* is a Gram-positive bacillus, and is the most abundant in the human skin. Although this species is known to be an anaerobe, most strains also grow well in aerobic conditions (that is, facultative anaerobe). They live in the 'colonisable layers', in hair follicles, and in sebaceous glands. The genome analysis has revealed that they possess a lipase gene that enables them to degrade and metabolise lipids produced from sebaceous glands (Brüggemann et al., 2004). This species prospers in humans in the skin, conjunctiva, and prostate, but strangely, it is rarely found in other host species. This species usually forms a two-cell structure similar to the shape of eyeglasses when cultured, and they also take this form in human skin.

At certain skin sites, other species are the major species. For example, *Micrococcus* species,

*Streptococcus* species, *Aerobacter* species, and *Proteus* species are cultured sometimes from the axilla and groin.

During the last decade, research on unculturable microorganisms using cultureindependent molecular techniques has been carried out on various human organs. The results were surprising; the microbiota of some organs such as the oral cavity and gut are dominated mainly by unculturable or difficult-to-culture species. With regard to the skin, Dekio et al. first reported such an analysis of the skin microbiota including a large number of unculturable species in 2005 (Dekio et al., 2005). The microbiota included 22 species that remained unidentified on the skin, in addition to the 11 known skin bacteria (Table 1).

physiological effects on the microecology of the skin. The scalp, face, neck, axilla, external genitalia, groin, and soles are examples of such sites. On the other hand, the microbiota seems to have little effect on the skin physiology at other sites with smaller populations,

Because the skin microbiota differs considerably across different sites of the human body, it is not possible to describe the microbiota of the entire body in a single entity. In general terms, however, the major population of the normal microbiota consists of coagulasenegative *Staphylococcus* species, *Propionibacterium acnes*, and *Malassezia* species. Coagulasenegative *Staphylococcus* species are aerobic bacteria, *P. acnes* is a facultative anaerobic bacterium, and *Malassezia* species are yeasts (a single-cell form of fungus). All of these microorganisms live on the surface of the skin and in the hair follicles (Fig. 1). No other human organ has such a unique composition of microbiota. These three groups of

microorganisms are retained in a balance between human immunity and each other.

Coagulase-negative *Staphylococcus* species are Gram-positive cocci. This group comprises *Staphylococcus* species other than *Staphylococcus aureus* and includes more than 10 species as *Staphylococcus epidermidis*. These bacteria grow under the aerobic condition and live in the colonisable layers of the skin. The term 'colonisable layers' here includes stratum corneum, the outermost barrier layer of the epidermis, and the outer thin section of viable layers of epidermis underneath the stratum corneum. These species can also grow under strict anaerobic conditions. This allows them to grow not only on the very surface of the skin but also deeper within skin layers where they compete for oxygen with other species. They are known to form grape-like clumps when cultured and normally also exist as

*Propionibacterium acnes* is a Gram-positive bacillus, and is the most abundant in the human skin. Although this species is known to be an anaerobe, most strains also grow well in aerobic conditions (that is, facultative anaerobe). They live in the 'colonisable layers', in hair follicles, and in sebaceous glands. The genome analysis has revealed that they possess a lipase gene that enables them to degrade and metabolise lipids produced from sebaceous glands (Brüggemann et al., 2004). This species prospers in humans in the skin, conjunctiva, and prostate, but strangely, it is rarely found in other host species. This species usually forms a two-cell structure similar to the shape of eyeglasses when cultured, and they also

At certain skin sites, other species are the major species. For example, *Micrococcus* species, *Streptococcus* species, *Aerobacter* species, and *Proteus* species are cultured sometimes from the

During the last decade, research on unculturable microorganisms using cultureindependent molecular techniques has been carried out on various human organs. The results were surprising; the microbiota of some organs such as the oral cavity and gut are dominated mainly by unculturable or difficult-to-culture species. With regard to the skin, Dekio et al. first reported such an analysis of the skin microbiota including a large number of unculturable species in 2005 (Dekio et al., 2005). The microbiota included 22 species that remained unidentified on the skin, in addition to the 11 known skin bacteria (Table 1).

such as arms, hands, and legs.

**2.2.1 Bacteria** 

clumps in skin layers.

take this form in human skin.

axilla and groin.

**2.2 Members of the normal skin microbiota** 

Fig. 1. Distribution of well-known skin inhabitants. (A) Typical hair follicle of the face. (B) Typical hair follicle of the trunk. SC, stratum corneum (a part of epidermis); E, viable portion of epidermis; D, dermis; H, hair; HF, hair follicle; SG, sebaceous gland; SwD, sweat duct; SwG, sweat gland. Note that the sweat duct and the sweat gland are considered to be sterile.

After this report, additional reports employing similar methods were published and a more complete picture of skin microbiota is emerging (Bek-Thomsen et al., 2008, Costello et al., 2009, Grice et al., 2009).

Microorganisms and Atopic Dermatitis 111

Interactions of humans and members of the microbiota or among the members themselves (Fig. 2) are difficult to investigate because the phenomenon is often quite complex. Research

Fig. 2. Scheme of interactions between a human host and microorganisms. SC, stratum corneum; E, viable part of epidermis; AP, antimicrobial peptide; FFA, free fatty acid. The text encased in red rectangles indicates adverse effects towards microorganisms, and the

**2.3 Characteristics of the microbiota in the skin of atopic dermatitis patients and its** 

Unlike the skin of healthy humans, the skin of AD patients is a 'rough ground' with less natural immunity. In a typical population of AD patients, the mutation in filaggrin gene (Palmer et al., 2006; Sasaki et al., 2008) results in impairment of the barrier function, and it allows the water content to evaporate. In addition, the sweat production is decreased because of the atrophy of the sweat glands. The resulting dry and rough surface allows easy colonisation of environmental bacteria. Moreover, a decrease in the amount of antimicrobial

The major outcome of AD is the presence of *Staphylococcus* species in very high numbers. The staphylococcal population in AD patients is about 10-100 times larger than that of normal individuals (Gloor et al., 1982). The *Staphylococcus* species here includes both

text encased in yellow rectangles implies beneficial effects for them.

peptides in the sweat exaggerates the lack of immune function.

**implications** 

**2.3.1 Bacteria in AD** 

**2.2.5 Possible interactions between a human host and microorganisms** 

is under way despite such difficulties.


Table 1. Example of novel bacterial species identified in facial skin by molecular methods (Dekio et al., 2005)
