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Skin - Microbiome

The Human Skin Microbiome  

The skin is known as the largest organ of the human body … and for good reason. Adults are known to have 8 pounds and 22 square feet of skin covering their bodies. It has an incredible range of versatile functions, that extend far beyond its cosmetic appeal (1). 

The skin is the major interface between the body and its external environment. In addition, it also serves as a host for a wide array of microscopic living organisms collectively called the skin microbiota or the skin microbiome. These are made up of different species of bacteria, fungi, viruses and even mites. Most of these organisms exist as commensals on the skin, living a symbiotic relationship with their hosts. Human skin can therefore be considered as an ecosystem of living organisms, occupying different habitats that are conducive to their growth (2). 

Where have skin microbiomes found their place?  

Structurally the skin is composed of two distinct layers, the outer epidermis and the inner dermis. Different body sites vary according to the texture and composition of skin components or appendages, like sweat glands, hair follicles and sebaceous glands. The distribution of these elements, give each area their unique characteristics or micro environments. They depend on different levels  of exposure to ultraviolet light exposure, pH, temperature, moisture, and sebum content. 

Skin sites are generally grouped as sebaceous or oily areas like face, chest and back ; moist areas like the bend of elbow, back of the knee or groin and dry areas like the palms or soles. Sweat glands help in thermoregulation through the evaporation of water, from the surface of the skin, giving rise to an acidic pH that makes the area unsuitable for the growth and colonization of certain microorganisms. Sweat also contains antimicrobial compounds like  free fatty acids and peptides, that discourage colony formation. Lipid rich sebum, secreted by the sebaceous glands, connected to hair follicles, gives a hydrophobic or water repellent property to the skin, that acts as both a lubricant and a shield against microbiome proliferation (3). 

The Age Factor : When do Microbiomes appear on the skin?  

Age has a tremendous effect on the microenvironment of the skin and, thus, on the colonizing microbiota.  When the fetus is still in the uterus, the skin is sterile. However, colonization occurs immediately after birth, during vaginal or caesarean deliveries.

Microbial communities of the skin and other sites are established and stabilized during the first years of life, as a newborns explore their environment and their immune systems mature.   

During puberty, changes in sebum production have been synchronous with increased levels of lipophilic bacteria on the skin. The difference in the sweat, sebum and hormonal secretions between men and women, at different ages,  have also been linked to the variation in microbiome colonies found between the genders (4). 

Sampling and Analysing Different Microbiota

Microorganisms that colonize the skin are extremely interesting for both microbiologists and dermatologists. Samples from the skin have been taken in order to study the flora extensively. The most common way to obtain  pure samples has been through culture -based studies, where a small sample of a microbiome  is grown and cultivated under controlled conditions, examined under a microscope, and tested with various methods to identify the type of organism present.

However, over time it became apparent that skin organisms have evolved so that they are able to grow in cool, dry and acidic environments. This gives rise to anaerobic bacteria that may be harboured in the skin, which are notoriously difficult to capture by traditional culture based methods. That is why the development of molecular techniques to analyse the organism’s genetic components, like RNA or DNA, has helped identify and quantify  microbiota that make up the skin’s flora. The discovery of the 16S ribosomal RNA gene which is present in all bacteria but not in eukaryotic cells like human cells, has made the classification of these microorganisms, using genetic sequencing a lot easier (5).

In addition,  genetic techniques using molecular studies, have also made it possible for us to recognize the skin’s microbiome  as being a partner, and not just a passenger, in mankind’s evolutionary journey.

The Origin Story : Using Genetic Sequencing to Analyse the Microbial Landscape  

Like all multicellular complex life forms, humans are hosts to an elaborate ecosystem of microbiota. Scientists have said that the body has a genetic landscape that includes both the human genome as well as that of the microorganisms that live in a symbiotic relationship with mankind, as we evolve. In fact some researchers also postulate that the commensal microbiota, through a symbiotic evolutionary process,  have provided human beings with genetic and metabolic attributes, like the ability to harvest and use inaccessible nutrients from the sources in the environment. New studies have revealed how the gut microbiota has co-evolved with mankind, as well as and how it manipulates and complements human biology in mutually beneficial ways (6). 

Research has determined that bacteria outnumber the cells containing  unique human DNA by  10 to 1. However, because of their microscopic size, microorganisms amount to only 1 to 3 % of the body's mass. (in a 200-pound adult, that’s 2 to 6 pounds of bacteria), but the role they play  in human health, is undeniable (7) 

Retrospective analysis has also shown that bacteria are effective evolutionary partners to mankind , because they are extremely flexible, adaptable , and most importantly, mutable. Prokaryotic bacteria have free floating genes, which they exchange with each other as well as with host organisms -like humans - quite frequently. The genetic exchange occurs through various methods and microbiologists have claimed that bacteria are like a continuum and are very unlike the eukaryotic cells with fixed genetic material (8). 

It is therefore not surprising that there may be  more 'foreign' DNA on and in the body, than there is human DNA. In fact, according to Professor Bob Knight from the University of California, "You're more microbe than you are human” because human cells make up only 43% of the total body cells count- the rest are microscopic colonists (9) 

Identifying Different Types of Organisms  

The human skin as an organ, is extremely diverse, as it imbibes characteristic features in different locations of the body, helping with both physiological and immune functions. The same variety extends to the microbiota that reside on the skin, from the Staphylococcal species that are found in humid areas like the bends of elbows and knees, to the Propionibacterium species that inhabit sites that are rich in sebaceous glands. In addition, more than 700 species have been detected in a healthy oral cavity (3)

Microorganisms (viruses, bacteria and fungi) and mites inhabit both the epidermis and the dermal layers of the skin, making themselves at home in and around sebaceous glands and hair shafts.  Rod shaped  Proteobacteria and round Staphylococcus species are the most common organisms found on the skin, that form close knit associations with other microbial species to build a thriving ecosystem. Commensal fungi such as Malassezia and viral particles live both freely as well as within bacterial cells. Skin mites, such as Demodex folliculorum and Demodex brevis, are some of the smallest arthropods and live in or near hair follicles (3).

Practical and Purposeful: Why are Microbiomes needed on the Skin?  

It is interesting to note that the relationship between the skin and flora, truly goes both ways. The innate and adaptive immune responses of the skin modulates the microbiome, but the microbiome also educates and trains the host’s immune system, thereby protecting the host from external infections from microorganisms (2)

The  majority of microorganisms , nearly 100 trillion of them are found in the intestine (10) 

They help in breaking down dietary products that humans would not otherwise be able to digest and play an important role in the production of essential nutrients like vitamin B and K. In the vagina, glycogen secreted contains a local, commensal population of lactobacilli that ferment the glycogen into lactic acid, maintaining an acidic pH and protecting the vagina from pathogenic bacterial infections. Commensals are known to build up the body’s defence against other bacteria by out-competing these foreign strains, for areas to invade as well as for the energy substrates (food) they would need to survive (8) 

Are there any side effects to the presence of microbiomes on the skin?  

The micro-organisms that make themselves at home on the surface of the skin, exist in a delicate balance with their hosts. Disruptions on either side of the equation may result in skin disorders or infections. Changes in the environment of the ecosystem,  genetic or lifestyle changes,  can leave the skin open to immune hypersensitivity disorders, like eczema or skin allergies. It may hamper the normal healing process, leading to chronic wounds like diabetic ulcers. Detrimental changes in the hosts immunity can also make them susceptible to microbial infections, that they could have easily fought off under normal circumstances.  

Each bacterial population has strains that can both help and damage the host’s body and skin. For example, Cutibacterium acnes can produce metabolites that prevent infection by pathogens. However, certain strains of C. acnes seem to have a causative role in acne (11).

Similarly , even though Staphylococcus aureus occupies the nostrils in 20% of the population, it can also be the leading cause of skin and soft tissue infections.

Propionibacterium acnes  is known to inhibit the invasion of pathogenic microbes like Staphylococcus  aureus and Streptococcus pyogenes through the production of short-chain fatty acids, like propionic acid and thiopeptides. However, changes in the chemical components of the skin barriers, also makes P. acnes the cause of acne vulgaris in  adolescents.  

Malassezia is a lipophilic fungi and represents  50%–80% of the total number of fungi species found as commensals on the skin, inhabiting oily areas such as the face, scalp, and back. They live in the sebaceous glands, feeding on lipids  found in human sebum. However, Malassezia has been implicated as a cause of dandruff, atopic dermatitis, tinea versicolor, and even psoriasis. This is due to the production of free fatty acids such as oleic acid produced by the fungi , which alters the permeability of the skin barrier, leading to inflammation of the skin or scalp (12)

Conclusion 

The human skin microbiome is a fascinating entity, serving as protectors and symbionts in the present, while it shows linking humans to their evolutionary history in the past. Molecular and genetic studies have highlighted the large role they play in our day to day lives , which is amazing considering … they are so minutely microscopic!  

Fun Facts : The Strange Scientific applications of Skin Microbiomes  

While skin microbiomes have demonstrated their use in human immunity with their protective functions, researchers have discovered novel ways to utilize their presence.  

1.     Use as a Forensic Tool 

A study conducted by the U.S. Department of Energy’s Argonne National Laboratory and the University of Chicago, called the “Human Microbiome Project” followed seven families with their pets over the course of 6 weeks. The participants swabbed the skin on the hands, feet and in their noses, as well as the common touch points in their houses, like door knobs, counter tops or light switches. These swabs were analysed to get an idea of the microbial populations living on them and around them (13). 

Lead researcher, Jack Gilbert, the microbiologist at the Argonne Lab who led the study, found that home and skin microbiome studies could potentially serve as a forensic tool. 

According to Gilbert, “Given an unidentified sample from a floor in this study, we could easily predict which family it came from. The research also suggests that when a person (and their microbes) leaves a house, the microbial community shifts noticeably in a matter of days. You could theoretically predict whether a person has lived in this location, and how recently, with very good accuracy,”(13) 

2.     How Gender affects the Microbial Ecosystem 

Scientists at North Carolina State University and the University of Colorado, Boulder, have analysed the DNA of microbiomes found on the skin and in the living spaces of forty families in the area. They discovered that in a home where there were more women than men, the bacteria lactobacillus, which is a major component of the vaginal microbiome population is found abundantly. Whereas, in homes where men outnumbered the women, Corynebacterium and Dermabacter strains were found inhabiting the skin. Corynebacterium is largely known to occupy the armpit and contribute to body odour, which may be at least one reason why bachelor pads and male dorm rooms or locker rooms have a decidedly pungent smell (14). 

3.     The Hygiene Hypothesis 

The “Hygiene Hypothesis” has often said that if ones’ environment is too clean, and if people have a high level of personal hygiene, there is a chance that they won’t be exposed to micro-organisms in their environment, both on their skin or in their gut. Exposure to these harmless  microbes are believed to exercise the human immune system, and helps it to stimulate a healthy immune response if the body is invaded by a pathogenic or harmful microorganism.  

Some scientists however, maintain that this theory does not hold true, as the body’s immune system, if kept healthy and robust,  is more than capable of fighting new infections, even without repeated exposure to infectious organisms. In fact, they believe that the “hygiene hypothesis” is misleading and detrimental to public health and sanitation. As arguments about the validity of the hygiene hypothesis rage on both sides of the aisle, it does raise the question : how clean is too clean (15)?

With the COVID pandemic in 2020, personal hygiene and hand washing has been in the limelight. Using excessive amounts of sanitizer has been known to disrupt the natural skin biome, leading to increased incidents of skin inflammation, which are dealt with using topical applications or moisturizers.  

Long-term changes in skin pH associated with hand-washing, is concerning, because some of the antibacterial characteristics of skin are associated with its normally acidic pH. Studies have shown that people who use strong antibacterial or antiseptic products to clean their skin, have a tendency to develop irritant contact dermatitis, especially with 10-45% of healthcare professionals, who face this as an occupational hazard (16). 

Jonathan Eisen, a microbiologist at the University of California at Davis, says, “In addition to killing off potentially beneficial bacteria, hand sanitizers could also contribute to antibiotic resistance. Even though they generally do not contain standard antibiotics, when microbes become resistant to some of the sanitizers this can make it easier for them to be resistant to more important antibiotics”(17) 

References  

1.    Skin. National geographic [Internet]. 2017 Jan 18 [cited 2021 Jun 19]; Available from: https://www.nationalgeographic.com/science/article/skin-1

2.    Grice EA, Segre JA. The skin microbiome [published correction appears in Nat Rev Microbiol. 2011 Aug;9(8):626]. Nat Rev Microbiol. 2011;9(4):244-253. doi:10.1038/nrmicro2537

3.    Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nat Rev Microbiol 16, 143–155 (2018). https://doi.org/10.1038/nrmicro.2017.157

4.    Giacomoni PU, Mammone T, Teri M. Gender-linked differences in human skin. J Dermatol Sci. 2009;55(3):144-149. doi:10.1016/j.jdermsci.2009.06.001

5.    Hugenholtz P, Pace NR. Identifying microbial diversity in the natural environment: a molecular phylogenetic approach. Trends Biotechnol. 1996;14(6):190-197. doi:10.1016/0167-7799(96)10025-1

6.    Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915-1920. doi:10.1126/science.1104816

7.    NIH Human Microbiome Project defines normal bacterial makeup of the body [Internet]. Nih.gov. 2015 [cited 2021 Jun 18]. Available from: https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body

8.    Katz SE. The art of fermentation: An in-depth exploration of essential concepts and processes from around the world. White River Junction, VT: Chelsea Green Publishing; 2012

9.    Gallagher J. More than half your body is not human. BBC [Internet]. 2018 Apr 10 [cited 2021 Jun 19]; Available from: https://www.bbc.com/news/health-43674270

10. Ruth E. Ley, Daniel A. Peterson, and Jeffrey I. Gordon, “Ecological and Evolutionary: Forces Shaping Microbial Diversity in the Human Intestine,” Cell 124:837 (2006).

11. Fitz-Gibbon S, Tomida S, Chiu B-H, Nguyen L, Du C, Liu M, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133(9):2152–60

12. Findley K, Grice EA. The skin microbiome: a focus on pathogens and their association with skin disease. PLoS Pathog. 2014;10(10):e1004436.

13. Home is where the microbes are: Home Microbiome Project announces results of study on household microbes [Internet]. Anl.gov. [cited 2021b Jun 17]. Available from: https://www.anl.gov/article/home-is-where-the-microbes-are-home-microbiome-project-announces-results-of-study-on-househol

14. Anthes E. What the dust in your house says about you. New Yorker (New York, NY: 1925) [Internet]. 2015 Nov 4 [cited 2021 Jun 18]; Available from: https://www.newyorker.com/tech/annals-of-technology/what-your-dust-says-about-you

15. Science X staff. The hygiene hypothesis is out of date and is undermining public health [Internet]. Medical Xpress. 2019 [cited 2021 Jun 19]. Available from: https://medicalxpress.com/news/2019-03-hygiene-hypothesis-date-undermining-health.html

16. Larson E. Hygiene of the skin: when is clean too clean? Emerg Infect Dis. 2001;7(2):225–30.

17. Maldarelli C. Is hand sanitizer bad for my microbiome? [Internet]. Popsci.com. 2019 [cited 2021 Jun 19]. Available from: https://www.popsci.com/is-hand-sanitizer-bad-for-my-microbiome