Human skin is constantly surrounded by an array of microbes. The surface has mechanisms to desist such colonization, as a defense preventing entry of potential pathogens. Nevertheless, complex communities of bacteria, fungi and viruses thrive on our skin. A newborn delivered by cesarean section is sterile but soon acquires its own resident flora within a few minutes. This initially consists of homogenous microbes over entire skin. However, with increasing environmental exposure and development of distinct moisture, temperature and glandular characteristics, individual skin habitats start arising with heterogeneous distribution of organisms. The mixture of organisms regularly found at any anatomical site is referred to as the normal flora, more appropriately as the “microbiome”.
An estimated 1 million bacteria, with hundreds of distinct species, inhabit each square centimeter of our skin. A thorough knowledge of the normal skin flora thus equips a clinician to predict the likely causative organism in disease states and also helps him focus on preservation of the cutaneous flora to prevent infections.
MICROBIAL SKIN FLORA
Studies have shown that the vast majority of skin bacteria fall into four phyla: Actinobacteria, Firmicutes, Bacteroides and Proteobacteria. However, within these phyla exist thousands of distinct species (Fig. 1). As organisms prefer designated environmental conditions, specific areas on human skin harbor specific flora. For instance, Propionibacterium species dominate sebaceous areas, such as the forehead, retroauricular crease, and back, whereas Staphylococcus and Corynebacterium species dominate moist areas, such as the axillae.4
Fig. 1: Microbiome composition on normal-appearing human skin.Source: Chen YE, Tsao H. The skin microbiome: current perspectives and future challenges. J Am Acad Dermatol. 2013;69(1):143-55.
Consistent with this idea of ecological niches, it has been reported that transplanting microbes from one habitat to another (such as from the tongue to the forehead), causes only a transient presence of tongue microbiota on the forehead with eventual return to the forehead microbiome.
The presence of three types of skin flora has been proposed. These include:
- The resident flora/commensals: It is the first group due to its compact attachment on the skin surface. Stratum corneum and upper epidermis are the common sites for the resident flora. This resident flora produces antimicrobial peptides (AMPs), which decrease the survival of pathogens on healthy human skin by two to three log fold. Sometimes, as the skin milieu is altered and under special circumstances like immunosuppression, in-dwelling catheters, 5etc. the resident microflora can become pathogenic and cause infections. The organisms which are commonly seen as resident flora are: Micrococcaceae, Coagulase-negative staphylococci, Peptococcus, Micrococcus, Coryneform organisms, Brevibacterium, Propionibacterium, Acinetobacter and Pityrosporum
- The second group is called the transient flora due to its free, unattached character. This group is more prevalent on the exposed skin surfaces
- A third group of organisms named temporary flora has been later identified which colonizes, the skin in a minority of individuals. These organisms need a combination of host and environmental factors to establish themselves and disappear under adverse conditions. A common example could be a physician, not using adequate universal precautions and exposed to infective organisms during wound dressing. He/she is likely to carry such flora. The organisms will stay till he is exposed and then gradually disappear.
The organisms colonizing human skin can be classified as follows.
Bacterial Flora
The important phyla have been listed above. Following are the details of few relevant organisms.
Micrococcaceae
This family includes staphylococci and micrococci.
Staphylococci
Coagulase-negative staphylococci are the most frequently found resident flora of human skin. At least 18 different species of staphylococci have been isolated from normal skin; the primary residents are S. epidermidis, S. hominis, S. haemolyticus, S. capitis, S. warneri, S. saprophyticus (most common in the perineum), S. cohnii, S. xylosus and S. simulans. Of these, S. epidermidis and S. hominis are the species recovered most frequently.
Staphylococcus aureus colonization is not very common on human skin, as it exhibits a great degree of natural resistance. Hence, apart from intertriginous areas and the perineum (where it touches 20% of the total flora), it is rare to find it colonizing human skin. Staphylococcus aureus carriage is most clinically relevant in the anterior nares with 20–40% of adults being nasal carriers. This carriage is even more common in diabetics, patients on hemodialysis, those with psoriasis and atopy, thus leading to a risk of recurrent pyoderma. Addressing this common carriage site often leads to resolution of pyoderma.6
Staphylococcus epidermidis colonizes the upper part of the body preferentially and constitutes more than 50% of the resident staphylococci of human skin. The forehead and the antecubital fossae carry S. saccharolyticus in 20% of adults.
Micrococci
Although less frequently present than staphylococci, at least eight different Micrococcus species have been identified from human skin. In order of prevalence, these are M. luteus, M. varians, M. lylae, M. nishinomiyaensis, M. kristinae, M. roseus, M. sedentarius and M. aggies.
Coryneform Organisms
The organisms of Corynebacterium genus are classically found in intertriginous areas. They are known as C. lipophilicus. Corynebacterium minutissimum, once thought to be a single organism distinguished by the ability to produce porphyrin, is now known to be a complex of as many as eight different species.
Propionibacteria
Propionibacterium species are nonspore-forming, anaerobic, Gram-positive bacteria that are normal residents of hair follicles and sebaceous glands. They are the most prevalent anaerobes amongst the normal flora and are also known as anaerobic coryneforms. They are divided into three species: P. acnes, P. granulosum and P. avidum.
Propionibacterium acnes, mostly seen on seborrheic areas on the body like skin of the scalp, forehead, and back, are almost universal (100% of adults subsequent to the puberty surge). With the puberty surge, the follicular concentration of P. acnes surges while P. granulosum is seen in lesser concentration. Propionibacterium avidum is localized to moist intertriginous areas.
Gram-negative Rods
They constitute only transient flora of human skin. Due to their high requirement of moisture for propagation and survival, desiccation inhibits their growth while intertriginous areas favor it. Enterobacter, Klebsiella, Escherichia coli and Proteus species are the predominant gram-negative organisms found on the skin. Acinetobacter is the major, gram-negative rod species on the skin. It may constitute about 25% of the total skin flora.7
Bacterial Interference and Competition
Due to the massive numbers and variety of microbial species on the skin surface, there is an intense competition for host resources and attachment sites. Many active mechanisms exist by which bacteria can impair or kill other microbes to ensure their survival. The fitter genes are thus naturally selected and passed on to the next generation.
Bacterial interference refers to antagonism between bacterial species during surface colonization and fight for nutrients. Bacteria have developed special mechanisms to interfere with the capability of other antagonistic bacteria to colonize and infect the host. The phenomenon of bacterial interference preventing colonization of nasal cavity by pathogens using Corynebacterium species, a common bacterium of the normal nasal flora, has been extensively studied. The artificially implanted strain of Corynebacterium species into the nares of 17 volunteers who were carriers of S. aureus, showed that the strain succeeded in eradicating the pathogen in 71% of the volunteers by a nonbacteriocin-like mechanism. A further study showed the capacity of viridans streptococci to hinder colonization of the oral cavity of newborns by methicillin-resistant S. aureus (MRSA). Furthermore, Lactobacillus species is the predominant microorganisms of the urogenital flora of healthy premenopausal women. Restoration of the normal flora by the use of locally or orally administered probiotics, based on strains of Lactobacillius species, could protect against recurrence of urinary tract infection (UTI) and bacterial vaginosis. Thus, it is hypothesized that using interfering bacteria for preventive and/or therapeutic purposes is a valid approach. The preservation of existing microflora by avoiding smoking and broad-spectrum long-term antibiotic regimens thus becomes an effective modality for preventing infections.
Fungal Flora
Fungi are commonly seen on the skin surface, with yeast being the predominant species.
Pityrosporum
Pityrosporum species, being lipophilic yeasts are more prevalent in seborrheic areas. Pityrosporum ovale and P. orbiculare are probably identical organisms that are prominent in sebaceous areas.8
Candida
Candida is present mostly in the oral mucous membranes (up to 40% of individuals). From this primary abode, it colonizes the vulvovaginal area. It has been estimated that 20% of asymptomatic healthy women of childbearing group carry the infection, but this can vary between 10% and 50%. When a suitable opportunity presents, these vaginal species can become pathogenic and present with vulvovaginal candidiasis. When present on the skin, C. albicans is the most common species found. Psoriatic, diabetic, atopic and immunocompromised patients have a higher colonization of Candida in their skin and mucosa.
Viral Flora
A recent analysis of the human skin virome in healthy individuals and cancer patients has confirmed a flora dominated by human papilloma virus (HPV), human polyomaviruses (HPyV) and circoviruses.
Human papilloma virus was initially thought to be only present in skin cancer patients, but subsequently it was found that healthy skin is also a habitat for a broad spectrum of HPV strains. A diverse community of HPV types has been identified on healthy skin, while identifying HPVs that were previously unknown.
The other major group of commensal human skin viruses is the HPyVs. Similar to HPV, HPyVs were originally studied in the context of cancer and were subsequently found on healthy human skin. The most common to human skin are HPyV6, HPyV7 and Merkel cell polyomavirus (MCPyV).
The other component of the human virome is the bacteriophage, about which little is known in the skin. Analysis of skin swabs from five healthy patients and one patient with a previous Merkel cell carcinoma lesion indicate that two families dominate cutaneous bacteriophage communities, the Microviridae and Siphoviridae. In the skin, bacteriophage communities have been suggested as mediators of resistance gene transfer between bacteria.
Parasites
Demodex (D. folliculorum and D. brevis), typically found on the face (cheeks, nose, chin, forehead, temples), scalp, neck and ears, is the most common ectoparasite on the skin surface. They are found in 10% of skin biopsies and 12% of follicles. Although D. folliculorum is the more common of the two mites, D. brevis has a wider distribution on the body.9
Prevalence of both species increases with age, with men being more heavily colonized than women (23% vs. 13%) and harboring more D. brevis than women (23% vs. 9%). Sebum appears to be essential for survival of Demodex; hence, they are infrequent in infants and children. Penetration of Demodex into the dermis or more commonly, an increase in the number of mites in the pilosebaceous unit (to >5/cm2), is thought to cause infestation, which triggers inflammation. Many facial conditions excluding acne but including rosacea, facial pruritus (with or without erythema), perioral dermatitis, Grover's disease, eosinophilic folliculitis, blepharitis, papulovesicular facial eruptions, papulopustular scalp eruptions and seborrhoeic dermatitis, etc. have elevated levels of Demodex. However, it remains unknown if Demodex is the underlying cause of these conditions or if Demodex mite density increases due to inflammation of affected follicles. Adding to the confusion is the fact that clinical presentation of Demodex infestation is similar to that of rosacea and seborrhoeic dermatitis with facial flushing/blushing, erythema, telangiectasia, scaling and facial skin roughness on palpation, and centrofacial inflammatory lesions. There has been a suggestion that Demodex dermatitis may in fact be distinct from rosacea and SD. Demodex is not easily detected in histological preparations; therefore, skin surface biopsy (SSB) technique with cyanoacrylic adhesion is a commonly used method to measure its density on the skin.