The Effects of Aging on the Human Skin Microbiome

Structure and Function of the Human Skin Microbiome

The skin is the human body’s largest organ, inhabiting microorganisms that vary between individuals and skin sites. Skin is cool, acidic, and desiccant. Its primary role is to act as a physical barrier to provide protection from foreign objects/organisms or hazardous substances. The epidermis specifically is the barrier in place for resisting penetration. Although the skin is continuously self-renewing, it is colonized by bacteria, archaea, fungi, and mites. These microbes are mostly harmless and beneficial to its host emphasizing their symbiotic relationship. Microbes provide the protection while the host provides the nutrients and habitat. It is essential to keep the host-microorganism relationship intact (Grice and Segre 2011). Dysbiosis, disruptions in balance, occur when this relationship is compromised by endo- and/or exogenous factors. The host’s genetic and environmental conditions play a major role when it comes to influencing the microbes’ functions. They vary by topography, endogenous and exogenous environmental factors. Immune responses control and regulate skin microbiota. In return, the skin educates the immune system of invaders and other factors that influence change. The 1.8 m² of skin folds create diverse habitats for microorganisms to flourish in; within the skin invaginations are ecosystems and niches. Sweat glands, sebaceous glands, and hair follicles are associated with a unique microbiota.

Microorganisms on the skin are complex, diverse, loosely organized, and vary from individual to individual and between skin sites. These microbes work together to form an ecosystem that is unique and variable with topographical diversity. Large populations of microbes are exposed to humidity, temperature, pH changes, and different environments. At least 19 bacteria phyla are present on the skin including Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes. Malassezia is the predominant fungus inhabiting the skin microbiome. Lipophilic microbes, occupying the sebum-rich areas, Arthropoda and Demodex mites, and viruses are all present in the ecosystem of the skin microbiome (Grice and Segre 2011). Although the skin viral microbiota is the least studied because most skin-associated viruses are not cultivable, a significant amount of information about the virome is known. It is generally considered to be pathogenic, but a complex viral flora exists, representing a significant part of the cutaneous flora. Research shows that the human viral microbiome is highly diverse with multiple polyomaviruses, papillomaviruses, and circoviruses on healthy skin (Foulongne et al. 2012). The dynamics and anatomical variations of skin viral microbiota have to be studied further.

Skin plays an important role in adapting whole-body physiology to new environments, including influencing the immune system and even emotions. Microbiota of the skin also have an essential role in the maturation of keratinocytes and host immune system implications. If harm is done to this protective barrier, not only can cutaneous infection occur, but other inflammatory non-communicable diseases can affect the host as well. Dysbiosis to the stratum corneum has been said to contribute to the development of allergic diseases (eczema and food allergies), psoriasis, rosacea, acne vulgaris, and the aging process (Prescott et al. 2017).

Host factors such as location, sex, and age contribute to the overall variability in microbes. Different environmental factors including occupation, type of clothing, antibiotic use, cosmetics, hygiene products and moisturizers are contributors to the diversity of the skin microbiome. There are physiological and anatomical differences of the cutaneous environments between human sexes. Gender influences the skin microbiota by the production of sweat, sebum, and hormones. Host age effects the structure and function of the skin microbiome. In utero, the surroundings are thought to be sterile; so is the skin. Colonization of microorganisms occurs immediately at birth whether it be vaginally or by c-section (Chu et al. 2017). Studies show that babies born vaginally have a microbiome that closely resembles their mother’s, and babies born via c-section have a microbiome more like the environment they were born in (operating room of hospital, home birth) (Hourigan et al. 2018).

Early-Life Skin Microbiome

There has not been much concluded about the formation of microbiota in utero. The uterus and the surrounding tissue, including the placenta, are considered sterile environments. It has been determined that the colonizers of the human microbiome make their debut immediately at the time of birth via the vaginal canal or cesarean section. Recent studies have shown that babies born vaginally have a microbiome that is more similar to their mothers. Microorganisms from the environment are the first colonizers in c-section babies causing their microbiomes to be less similar to their mothers compared to babies born vaginally. The studies mentioned previously focused on the gut microbiota. When it comes to the formation and differences in the skin microbiome, mode of delivery was not a determining factor (Capone et al. 2011).

The composition, structure, and function of the skin microbiota are rapidly colonized at birth then gradually change in the first years of life. It changes gradually as the infant ages. Newborns transition from an environment that is mostly sterile and aqueous to a gaseous surrounding where they are in constant contact with microbes. The skin microbiomes of infants and adults differ in biochemical composition, structure, and function. As humans age, their microbiome diversity and stability increases. These bacterial communities contribute to homeostasis and control inflammatory responses, which in turn modulates immune responses. Infant skin is sensitive and prone to inflammatory conditions such as eczema, diaper dermatitis, and candidiasis. Instability in infant microflora could lead to abnormal skin development if the normal microbiota is not established. One study assessed the overall bacterial diversity and richness of infant skin from three different sites (forearm, buttock, and forehead). It was concluded that the number of genera in the three sites was not significantly different during the first year of life, but community richness was significantly increased with age (Capone et al. 2011).

Early-life skin microbiota in infants are dominated by Staphylococcus and resemble that of adults with moist skin. Bacterial communities, especially those of the Staphylococcus genus, contribute to homeostasis and promote early immune response (Capone et al. 2011). Although they have been found to maintain evenness of the skin microbiome, it was concluded that colonization of S. Aureus may actively contribute to the development of atopic dermatitis (Meylan et al. 2017). Other early colonizers were discovered to be a part of the infant skin microbiome (Streptococcus, Enterococcus, and Candida). The latter two bacterial species play an essential role in the development of the skin microbiome as a neonate. Maturation is critical for preventing colonization with pathogens which could lead to infant sepsis, especially in preterm infants. A recent article suggests that gestational age (number of weeks a baby has been in the uterus) has an influence on the maturity of skin structure and function (Pammi et al. 2017). Gestational age is directly proportional to bacterial richness. Another study found that infants are colonized by few fungal taxa and there was no clear maturation over the first year of life. Further mycobiome studies are needed to determine the presence and significance of fungi in the skin microbial community in early-life (Ward et al. 2018).

Adolescent-Adulthood Skin Microbiome

Human skin continues to change as one ages. The dynamics of the skin microbiome shift as the host grows from infant to child into an adolescent. As humans approach the ages of 10 – 16 years, puberty begins to take place. This is initiated by hormonal signals from the brain to the ovaries in girls and the testes in boys. The influx of hormones can lead to not only physical changes (menstruation, deepened voice, growth spurt), but also skin disorders due to sudden changes in the skin microbial community. Tinea capitis, acne, seborrheic dermatitis, atopic dermatitis, and dermatophytosis are skin disorders found in postpubescent males and females. A study done by Jo et al. in 2016 found that commensal and pathogenic fungi drive cutaneous diseases such as those mentioned previously. This study focused on the fungal communities, skin mycobiome, in children and adults. Compared to adults, prepubescent children have less sebaceous skin but are more diverse in terms of relative abundance and fungal community diversity. Dermatophytes, pathogenic skin fungi, are amongst the fungal communities present. The mycobiomes of the children in this study were colonized by Malassezia. M. globosa was the predominate species present. It is known to be present on the tops of skin and scalp of children. During sexual maturation, gender may affect the mycobiome differently for males and females. Malassezia was enriched in girls, whereas Epicoccum and Cryptococcus were enriched in boys. In adults, the skin of both genders was predominated by Malassezia. Jo et al. concluded that age-dependent differences occur in skin physiology and the mycobiome. There is a strong association between sexual maturation and the composition of the mycobiome. Activation of sebaceous gland activity during puberty may lead to the colonization of Malassezia, an obligatory lipophilic fungus. The presence of lipid-preferring fungi on the skin of postpubescent humans is indicative of the mycobiome changing and maturing to be more adult-like (Jo et al. 2016).

Similar to the fungal microbial community, significant shifts in the skin bacterial microbiota have been associated with sexual maturation. Shifts in microbial communities have the potential to alter skin health and result in cutaneous diseases (eczema, acne vulgaris, plaque psoriasis). Postpubescent children and teens are prone to the previously mentioned cutaneous diseases, especially when these shifts occur. Bacteria on the skin play an important role in homeostatic regulation and host immune networks during this time. Colonizing microbes have to keep in constant contact with their host to ensure equilibria. Sebaceous glands, Propionibacterium acnes, and follicular keratinocytes are the three main components involved in the development of acne.  Newly forming sebaceous glands in adolescents going through puberty experience increased sebum production. Excessive sebum production leads to the development of acne lesions. According to a study by Drena et al. (2017) Proteobacteria, Firmicutes, and Staphylococci are the most abundant bacteria present on the skin of acne sufferers. The proportions of those bacteria increase significantly with acne severity.

P. acnes and acne vulgaris have a well-established relationship. Drena et al. found that there are natural differences between the colonizers in the sebaceous glands and on the skin surface. Cutaneous bacterial communities trigger acne when the microbes are unable to sustain a homeostatic environment. Although there has been negative light shed on P. acne, it is a commensal bacterium in certain aspects. It has a physiological role in inhibiting the invasion of pathogenic bacteria such as Staphylococcus aureus and S. pyogenes. This inhibitory mechanism does not allow the host to be penetrated by these harmful bacteria. P. acnes maintains the natural pH of skin and sebaceous glands. It hydrolyzes triglycerides, which in turn aids in innate immunity because free fatty acids are released. Species of Staphylococcus, especially S. epidermis, were found to be the predominant bacteria on the skin in this study. S. epidermis functions to control the growth of P. acnes colonies on the skin and sebaceous glands; it also inhibits P. acnes-induced inflammation in the skin. S. epidermis aids in balancing the immune system and the equilibrium of skin microbiota, which leads to healthy skin. It is essential to establish and maintain this system of mechanisms to promote healthy, acne-free skin, especially in evolving teenagers (Dreno et al. 2017).

Late-Life Skin Microbiome

As mentioned beforehand, the interconnection of skin microorganisms is everchanging, adapting to many different factors: age being one of them. Diet and living conditions are great influencers of the skin microbiome of older individuals. Most studies focused on the changes that take place within the gut microbiome, but there are significant alterations that take place when humans age. A study done by Roghmann et al. in 2017 compared the nose, throat, and skin microbiota of older people in nursing homes versus those out in the community. These two environments are different in their levels of exposure to certain substances and microorganisms. Nursing home individuals are known to have a greater prevalence of colonization of multidrug-resistant microorganisms, especially Gram-negative bacteria. The specific skin over the subclavian and femoral veins were chosen for this experiment because these sites harbor the bacteria that commonly cause health care-associated infections. The subclavian site was prevalent in S. epidermidis, Propionibacterium acnes, and Achromobacter. S. epidermidis, Corynebacterium, and Achromobacter were prevalent in the femoral site. Proteobacteria was less prevalent in the nursing home individuals compared to those living in the community. Firmicutes, Proteus, E. coli, and Enterococci bacterial species were more prominent in the nursing home group. The elderly individuals who either showered or bathed were less likely to have Enterococcus and more likely to have Enhydrobacter and Stenotrophomonas. The skin site in the femoral area had frequent abundance of Enterobacteriaceae and P. aeruginosa in nursing home participants. These bacteria are commonly found in stool and can easily contaminate the skin in that area. The nursing home participants were less likely to have showered or bathed within 12 hours of the skin samples being taken. This would have led to a higher frequency of bacteria associated with poor hygiene indicating that it is reasonable to improve hygiene in nursing homes. Bathing patients with antiseptics (Hibiclens, chlorhexidine gluconate) will decrease their chances of acquiring and transmitting multidrug-resistant microorganisms (Roghmann et al. 2017).

There was a decrease in abundance of specific Proteobacteria in the nursing home participants in both skin sites in comparison to the participants who lived out in the community. Those included Pseudomonas, Burkholderia, Enhydrobacter, Stenotrophomonas, Achromobacter, and Acinetobacter which are significant components of the skin microbiota. Although they are considered beneficial to the host, they have been reported to cause infection in immunocompromised hosts (individuals with cystic fibrosis or cancer patients). The specific Proteobacteria named above are said to be found in the water supply. Residents of the nursing home may be less exposed to them because it was reported that they shower less frequently than individuals living in the community. The fact that older adults have less oily skin and sweat less frequently than their younger counterparts are other factors that could explain the decreased abundance. According to this study, it is too soon to classify these particular Proteobacteria as beneficial or harmful to the elderly host.

A recent study done in May of 2018 focused on the shift in skin microbiota of Western European women across aging. The women in the younger group were aged 21-32 years old and the women in the older group were aged 54-69 years old. Skin microbiota reaches an equilibrium specific to each individual at adulthood. Individual-specific and external factors play a significant role in influencing the skin changes as one ages. Other factors of influence include gender, environment, lifestyle, and hygiene preferences. Other recent research involving the effects of aging focus on the physiological changes and the ecological alterations. These studies concluded that the diversity and taxonomic composition of skin microbiota is greatly influenced by the aging process (Jugé et al. 2018). The study mentioned by Juge and colleagues found that the older adults had more alpha diversity and species richness than the younger adults. The two groups, young and old, share the same species but in different relative abundances. There was an increase of abundance in Proteobacteria and a decrease in Actinobacteria and Propionibacterium. These results were in concordance with other recent studies. Propionibacterium is a lipophilic microorganism that resides in sebum-rich areas of the skin. Changes in hormonal levels in older individuals are known to lead to decreased sebum production. There was an increase in the abundance of Corynebacterium, a commensal species, in the elder population. An increase in this species has been associated with cutaneous infections and skin barrier defects. Changes in sebum secretion, pH, and lipid composition all contribute to skin microbiome alterations in the elderly. Along with these changes, natural immune defenses become less effective with age. This can lead to an increase in pathogen susceptibility and impairment to skin barrier function. The study concluded that the differences in the skin microbiomes of young versus elder women is linked to physiological changes and external factors.

Conclusion

The human body’s organ inhabits many different microorganisms that vary throughout its expansive area. Its interconnected microbial communities form essential relationships that are mostly symbiotic, but some are parasitic. These connections are important in the structure and function of the human skin microbiome. Many factors have roles in the alteration and impact of the self-renewing skin microbiome. The focus of this review was on the aging process and how it affects the cutaneous microbial community.

Rapid colonization of microorganisms on the skin take place soon after birth and lead to functional changes. Skin during the periods of early-life differ from adult skin in biochemical composition, structure, and function. It becomes more stable over time. As humans grow from babies to school-aged, pubescent individuals they cutaneous dynamics continue to shift. The hormonal changes that initiate puberty cause significant alterations to the skin microbiome, especially in response to the newly forming sebaceous glands. A few common cutaneous disorders (acne vulgaris, eczema, tinea capitis) have been associated with this shift during sexual maturity and into adulthood. Later in life, one’s skin gains a more diverse interconnection of microorganisms that work to maintain barriers and protect the host against pathogens. Even more changes in hormones, pH, and sebum secretion are observed in this stage of aging; they have a role in the structure and function of the skin microbiome of older adults. Overall, the skin is influenced by many factors to include gender, environment, lifestyle, hygiene preferences, and age. It is important to continue generating new studies and research on all aspects of the skin microbiome and the components that contribute to its everchanging microenvironment.

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