#21: Scratching the surface: The microbiology of human skin and contamination control

Understanding the skin microbiome is of great importance across many fields, not least in playing a role in precision medicine initiatives and with understanding the pathophysiology of skin diseases.

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Characterizing the skin microbiome is also of importance for cleanroom microbiology, from helping to pinpoint potential origins of contamination to understanding the hazards presented by different individuals.

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The human microbiome of the skin has been the subject of considerable research for past 15 years (arguably beginning with a seminal paper by Grice) (1). This has been made possible through the analysis and characterization of 16S ribosomal RNA genes, which reveals a greater diversity of organisms than was ever possible by culture-based methods.

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In this week's newsletter, we’ll take a look at some of the interesting findings that have arisen from human skin microbiome research, put these into context, and see what lessons we can draw in terms of contamination control.

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Diversity

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The skin is our biggest organ (the average human has around 1.8 square meters of skin). Differences in temperature, moisture, pH, salts and so on lead to varying ecological niches and hence the presence of site-specific microbial communities. The most influential factors identified by microbiome researchers are: sebum, trans-epidermal water loss (TEWL), moisture and pH.

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As such, there is no universal skin organism (no taxa have been observed to be present among all areas of the skin) (2). However, some types of organisms predominate and specific niches tend to have ‘signature taxa’ (commonly representative organisms) (3).

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By site

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The primary differences in bacterial content relate to different body sites, influenced by their different physiologic characteristics, especially sebaceous, moist, or dry (4).

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The most diverse communities tend to be the forearm and the least diversity is found behind the ear. In terms of physiologic characteristics Cutibacterium (Actinobacteria) predominate in sebaceous areas, Corynebacterium (also of the phyla Actinobacteria) and Staphylococcus (Firmicutes) spp. predominate in moist areas; whereas the dry areas exhibit the greatest amount of diversity.

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Based on Grice’s work, in terms of a comparison between people, it is with the microorganisms residing behind the knees, on the elbow, and behind the ear that are more similar.

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Between individuals

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There are many areas of commonality between people, especially those within the same biogeographical areas or who commonly share the same space. However, there are also differences between people in terms of the balance of different organisms within different niches. Sometimes this is a factor of health and disease (especially with dermatitis in this context). In other cases, differences can be detected in terms of body odor (as with why one person has an odor whereas another does not?) Body odor arises through the microbial conversion of sweat to malodorous products in the form of the production of volatile organic compounds, including volatile fatty acids and thioalcohols. There are many organisms capable of this, although an imbalance of Corynebacterium striatum, Corynebacterium jeikeium and Corynebacterium bovis each has a high association with odor development.

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Environment

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With the outer layers of the epidermidis, the environment within which people reside or come into contact with influences the microbiome (5). Hence, there will be variations according to geography, urban and rural dwelling, personal hygiene and so forth (with hygiene, too frequent washing can disturb the skin barrier resulting in skin irritation, leading to greater microbial release) (6). The degree of change through geography should not be overly-exaggerated, however; the skin-associated microbiome does not seem to be influenced by long-term changes in immediate habitat for human populations. For example, when families move between different houses (7). Another factor of similarity is with how closely people live with each other, in terms of contiguous living.

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Perhaps more important than geography is the area that people spend most of their time in. Those who spend most of their time indoors will have microbiomes are predominantly human-derived, whereas outdoor workers will be subject to soil, aquatic and host-associated microbial sources that could alter their skin microbiome composition.

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Other environmental factors include cosmetic use (which may also account for some sex differences, see below) or sun exposure. The microbiome also shifts in response to skin injury.

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Health and disease

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Skin-resident microbes contribute to the establishment of cutaneous homeostasis. Often there is a mutualistic relationship between microorganisms and when in balance this keeps pathogens in check (8). However, an imbalance can modulate inflammatory responses or trigger pathogenicity.

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Some treatments can also be disruptive, with certain antibiotics shown to cause disruption and imbalance to the skin microbiome (9).

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As we age

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Studies of the cutaneous microbiome (microbial and genomic components) across different age groups indicate the dynamic nature of the skin microbial communities (the microbiota). Here shifts in community structure and diversity occur through to old age.

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For example, a set of studies has shown a lower abundance of Actinobacteria (species like Cutibacterium) and an increase in Firmicutes, Bacteroidetes, and Proteobacteria, depending on the skin site, as people age. The reduction in Cutibacterium appears connected to a decrease in decrease in sebum secretion.

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The areas subject to greatest change as people age are the forearms and the scalp (10).

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By sex

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Biological males and females exhibit differences with their skin microbiota. This is also something that is dynamic, also altering through ageing. For example (11):

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·???????? Species richness in men is lower females.

·???????? Cutibacterium abundance is greater in men (due to there being more terminal hair follicles and sebaceous glands).

·???????? The abundance of Staphylococcus (especially with the nares) and Alloiococcus (ears) is greater in females than in males.

·???????? Anaerococcus is higher in males than in females (an anaerobic organism more likely to originate in the nasal cavity).

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Why might such sex differences occur? Researchers suggest this is due to physiologic differences between male and female skin microenvironments, such as hormones, metabolism, perspiration rate, lipid content, and pH (men generally have a more acidic skin surface than women). Other factors are sebum production, skin thickness and hair growth (13). There have been several observations that changing room frequented by, or exclusive to, males tend to have higher microbial counts than those used by females (13).

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Avoidance of cosmetics

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Those going into cleanrooms will be used to the requirement not to have put on cosmetic products if they are to enter a cleanroom that day. As well as particulate generation, there are some sound reasons for this in terms of microbial control. Some cosmetic products have a strong association with microorganisms. For example, deodorant and foot powders increased bacterial diversity. Other personal care products produce highly individualized responses.

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There is some importance with the activity of thoroughly removing cosmetics from the skin, given that with some specific beauty products remain detectable with half-lives of 0.5–1.9?weeks later (14).

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What does the mean for contamination control?

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Given that during a 24-hour period, a person loses almost five billion skin cells, a high proportion of these will be microbial carrying particles (15).? The specific microbial risk depends upon the specific site and the controls in place in terms of cleanroom gowning. The consensus of research is that differences with sebaceous, moist and dry regions are the most important factors influencing community structure.

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This means we need to continue to pay special attention to factors like (16):?

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·???????? Ensuring high air change rates in changing areas,

·???????? Having robust gowning training procedures,

·???????? Assessing the quality of cleanroom certified undergarments,

·???????? Stipulating maximum times for wearing cleanroom suits,

·???????? Rejecting any suits for loss of integrity

·???????? Ensuring that we cover the forehead, wear gloves and masks.

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It is important to reconsider the necessity of good gowning and of environmental control,

Together with minimizing the opportunities for operators to interact with product.

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Many of Tim Sandle’s publications are available on ResearchGate.?

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References

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1.????? Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC, et al. Topographical and temporal diversity of the human skin microbiome. Science (New York, NY). 2009;324(5931):1190–2

2.????? Huse, S., Ye, Y., Zhou, Y. & Fodor, A. A core human microbiome as viewed through 16s rRNA sequences clusters. PLoS ONE https://dx.doi.org/10.1371/journal.pone.0034242

3.????? Li, K., Bihan, M., Yooseph, S. & Methe, B. A. Analyses of the microbial diversity across the human microbiome. PLoS ONE https://dx.doi.org/10.1371/journal.pone.0032118

4.????? Leung MH, Wilkins D, Lee PK. Insights into the pan-microbiome: skin microbial communities of Chinese individuals differ from other racial groups. Sci Rep. 2015;16(5):11845

5.????? Bay L, Barnes CJ, Fritz BG, Thorsen J, Restrup MEM, Rasmussen L, et al. Universal dermal microbiome in human skin. mBio. 2020;11(1):e02945–19

6.????? Rocha LA, Ferreira de Almeida EBL, Gontijo Filho PP. Changes in hands microbiota associated with skin damage because of hand hygiene procedures on the health care workers. Am J Infect Control 2009; 37: 155–159

7.????? Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM, Scott NM, et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science. 2014;345(6200):1048–52

8.????? Chen YE, Fischbach MA, Belkaid Y. Skin microbiota-host interactions. Nature. 2018;553(7689):427–36

9.????? Leccia MT, Auffret N, Poli F, Claudel JP, Corvec S, Dreno B. Topical acne treatments in Europe and the issue of antimicrobial resistance. J Eur Acad Dermatol Venereol 2015; 29: 1485–1492

10.? Shibagaki N, Suda W, Clavaud C, Bastien P, Takayasu L, Iioka E, et al. Aging-related changes in the diversity of women's skin microbiomes associated with oral bacteria. Sci Rep. 2017;7(1):10567

11.? Ying S, Zeng DN, Chi L, Tan Y, Galzote C, Cardona C, et al. The influence of age and gender on skin-associated microbial communities in urban and rural human populations. PLoS One. 2015;10(10):e0141842

12.? Giacomoni PU, Mammone T, Teri M: Gender-linked differences in human skin. J Dermatol Sci. 2009, 55: 144-149. 10.1016/j.jdermsci.2009.06.001

13.? Smith, L., O'driscoll, N. and Lamb, A. 2020. Gender influences bacterial contamination of reusable cleanroom operators’ garments following wear. European journal of parenteral and pharmaceutical sciences, 25(2): https://doi.org/10.37521/ejpps25202

14.? Lloyd-Price J, Mahurkar A, Rahnavard G, Crabtree J, Orvis J, Hall AB, et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature. 2017;550(7674):61-6