Microbiome: to learn more to look good

Ben Teoh R&D Director – Ante Cosmetic

Microbiome is becoming a household word and is referring to as a mix of bacteria, yeasts and parasites that live on our skin, in our nose and trachea, and in our gut from our mouth to our anus. The mix of these bacteria, yeasts, and parasites is closely linked to weight, mental health, autoimmune health, blood pressure, diabetes, heart disease, and even cancer, and therefore, worth knowing more to enhance our general well being.

These microbes are in microscopic forms of life invisible to the naked eye. And there are a variety of microbes: fungi, mites, protozoa, and bacteria to name a few. Now, the word “bacteria” can automatically conjure up unpleasant images of illnesses and germs. But you probably know by now that a lot of bacteria are healthy.

In fact, there’s a good chance we have taken a probiotic at one time or another to encourage the growth of these healthy bacteria. That is because bacteria are essential for human functioning – they aid digestion, strengthen the immune system, and help maintain the health of our skin.

Skin Microbiome

Our skin is considered to be the largest organ, with a surface area of approximately 1.8 sq. m. It protects us from the environment, is important for thermoregulation and is definitely key for our appearance. Within our skin ecosystem, we are not alone in our skin—millions of small companions are settling on our skin’s surface: microbes. Our body’s ecosystem known as a “microbiome” is kind of a smaller version of an ecosystem. The human microbiome consists of small organisms called “microorganisms” or “microbes” and it is estimated that an astonishing 10 to 100 trillion microbes make up their home in the human body.1 On average, there are ten times more microbial cells than there are human cells in the body.2

A microbiome is (in other words) simply the collection of microorganisms in a particular place. The gut microbiome is the entire collection of microorganisms in the gut, and similarly, the skin micrombiome is simply all of the organisms present on the skin.

The term “microbiota” is also used to describe these organisms and specifically means: “the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space.”

Because research has proven the importance of the gut microbiome, and many of us now understand the importance in consuming probiotic rich foods and the over usage of antibacterial soaps is bad for gut health. It turns out that these same factors also affect the microbiota on our skin and protecting it may be just as important. As a result, most skin problems mainly from acne to eczema, are likely affecting the skin microbiome.

Skin Associated Lymphoid Tissue – SALT

Skin was in the past thought as only a physical barrier from the outside world, but the existence of skin-associated lymphoid tissue makes it much more. Researchers estimate that these lymphocytes exist on the skin in a 1:1 ratio with bacteria. These immune cells are capable of sensing and dealing with a great deal of bacteria on their own. They also communicate with lymph nodes within the body. These lymph nodes carry immune signals to the rest of the immune system and help determine the body’s appropriate response.3

In summary, our skin contains trillions of lymphocytes that are cells protecting our body and its perimeter, radioing information on impending attacks to the main base known as our immune system.

Skin microbiome occurs during and right after birth

A healthy skin microbiome apparently starts during and shortly after birth with a flurry of immune activity. Unfortunately, many of the modern practices surrounding birth may have a dramatic and unfortunate impact on gut bacteria. Researchers at the University of California San Fransisco have found that an important part of the skin microbiome is established within days of birth. Mainly, within days of birth, there is a large amount of T-cell activity that creates tolerance in the immune system to the bacteria on the skin. This is a critical factor in the immune system’s understanding- to stop attacking the normal and healthy bacteria on the skin.

However, the wide use of antibiotics during labor may have caused big unintended consequences to the microbiome. As such, that could be part of the reason we are seeing a rise in skin related disorders and for the reason, research is even more critical. The research indicates that if this window is missed, it is difficult or impossible to recreate as an adult giving rise for the belief to hold off on a baby’s first bath for the first few days.

Skin & Gut microbiome Interaction

None of our body’s microbiome exists in a vacuum, and it is important to continue to understand the different parts of the biome and their interaction. As the study above indicated, trillions of lymphocytes interact with the rest of the immune system via lymph nodes. Just like the bacterial organisms in the gut, they comprise a valuable part of the immune system. As such, this may give us a reason to rethink the use of antibacterial or antimicrobial products.

There is already a fair amount known on the innate immune system responding to the skin’s microbiome, but very little about the adaptive immune response to microbes in the skin owing to the challenges of genetically manipulating bacterial species native to the skin. Creating one of the first genetically engineered commensal skin microbes, recent studies introduced an antigen linked to a fluorescent protein, Epi-2W, into Staphylococcus epidermidis, found in abundance both on human and mouse skin. Such could then precisely track the immune response to the tagged antigen in a mouse model.

With S. epidermidis applied to the skin of adult mice not previously exposed to such bacteria, the animals developed an effector T-cell response without overt skin inflammation, suggesting that the immune system registered the microbe as a mild pathogen. But exposure to the bug in adulthood was not enough to establish immune tolerance of this species; however, if these same mice previously colonized with S. epidermidis were subsequently subjected to minor skin abrasions along with an application of S. epidermidis, their immune systems mounted responses that included inflammation and activation of T cells against the bacteria.

Because the microbiomes of the skin, gut, and other organs are established prior to and right after birth, the researchers reasoned that the immune system may set up tolerance to commensal bacteria only early in life. So the team repeated the same experiments using one-week-old mice. The researchers first exposed the skin of neonatal mice to S. epidermidis and then subsequently challenged these mice with the same bacteria plus skin abrasion four weeks later. The challenge resulted in a minimal inflammatory response and few activated T cells against the commensal bacteria, suggesting that the immune systems had established tolerance to the microbe.

The research has proven that the skin develops tolerance to S. epidermidis and, importantly, identified a window in early life when this happens.

A closer analysis of the neonatal mice showed a parallel influx of regulatory T cells unique to the skin during the first two weeks after birth. This colonization of the skin by regulatory T cells, immune cells that dampen the responses of effector T cells: This was required for tolerance to S. epidermidis, the researchers found.

That there is an abrupt wave of [regulatory T cell] infiltration into neonatal skin occurring at a defined period and that this window dictates the achievement of commensal-specific tolerance becoming an important finding.

A major clinical implication of this study is giving antibiotics to a child in early neonatal life is likely a disservice because this will limit the amount and type of bacteria seen by the adaptive immune system and this could be linked to the development of autoimmune, inflammatory skin diseases later in life.

A critical issue arises whether introduction of tolerance to commensal bacteria is possible following the closing of the developmental window described in the study. This could be an important aspect to explore on how to induce commensal-specific tolerance in patients who have not acquired it.

Research on characterizing the wave of T regulatory cells to the skin after birth in human is underway while, the understanding on whether these cells help maintain immune tolerance to commensal skin microbes. The results would help us understand more the skin development and the method on maintaining our skin microbes.

However, the greatest challenges in understanding human microbiome projects are the understanding of which microbes cause infection and which are tolerated. And the research has given us the learning, that there are critical time frames where the immune status is set that alter reactions to microbes later in life.4

Recent advancement in microbiome analysis techniques revealed a much higher bacterial diversity on skin than previously detected by culture-based methods. As an example, studies by companies on acne prone skin have revealed bacteria from six phyla, between 80 families and 500 different species – this is only a fraction of what can be found in normal skin. Furthermore, skin of different ethnicities and of peoples who live on different continents may even harbor greater microbe diversity. Skin’s microflora is important to guard against potentially harmful materials. By means of occupying the skin niches, settlement of germs is strongly reduced. Additionally, sweat plays an important part of providing the best conditions for this beneficial microflora that creates a slightly acidity pH on the skin surface.5

Microflora produces a human being’s typical scent and in moist areas, in particular, apocrine sweat glands secrete a special sebum composition in which Staphylococci, Corynebacteria and Bacilli degrade sebum, dead cell material and components of the skin surface. These produce body odor by releasing their metabolites.

Imbalanced Microflora condition referred to as dysbiosi, may cause skin problems such as acne, atopic eczema and fungal infections. Despite this, the microflora is not the root cause of skin problems, but rather a reaction to dysregulated skin functions.

Basically, microorganisms need food being a typical respond of the skin. In the case of greasy skin, huge quantity of sebum is available to support the excessive growth of Staphylococci and Propioni bacteria, and the latter being trapped in anaerobic zones of clogged skin pores owing to hyperkeratinization, are the main drivers of acne vulgaris and the formation of inflammatory spots.

Excess sebumlation occurs as the sebaceous duct is filled with excess sebum and dead keratinocytes. Oxidation turns the greasy texture of sebum into a wax-like consistency, while melanin of dead keratinocytes oxidizes and becomes black, and this in turn is recognized as blackhead comedones. The following sebum will be trapped in an anaerobic tube. These are the best condition for the colonization of Propionibacterium acnes (P. acnes), an anaerobic Gram-positive bacterium settling on the sebum-rich parts of the body.

With an estimated density of 100–1,000,000 per square centimeter on the skin, P.acnes accounts for approximately half of the total skin microflora and may represent more than 90% of the microflora in acne conditions. It feeds on lipids and secretes metabolites such as porphyrins and lipopolysaccharides; all while attracting immune cells, which aim to fight the bacterial infection.6 In the late stage of an acne pustule, the epidermis around the hair shaft ruptures to create scarring in the skin.

Therapies on Acne & Oily Skin

Pharmacologically, there are 2 major strategies to fight oily skin and the development of acne.

1. the reprograming of sebocytes to produce smaller amounts of sebum i. e., the feeding ground for P. acnes.

2. to use strong cleansing products containing benzoyl peroxide to control the excess settlement of bacteria. This therapy targets P. acnes in particular; however, the entirety of the skin’s microflora is affected due to the radical nature of benzoyl peroxide. Due to this, benzoyl peroxide therapies should only be utilized under medical supervision. Furthermore, the regular use of benzoyl peroxide may provoke dry skin.

Antibiotics also are commonly used to fight a severely imbalanced microflora. However, the use of non-specific broad-spectrum antibiotics increases the risk of generating resistant Staphylococcus aureus strains, which according to latest investigations, also settle in pores and pimples.7

Cosmetic solutions for acne-prone skin can only mimic one’s dermatological armory to prevent the aggravation of a mild condition. And since a healthy microflora is important to reduce the growth of deleterious species, it is crucial to choose intelligent molecules that target a specific sub-population of bacteria; in the cases of oily skin or moist areas, these targets are predominantly P. acnes or Corynebacterium spec., that create malodor, respectively.

Conclusions

It is important to reduce the number of unwanted bacteria in favor of a balanced microbiota to maintain a healthy skin. Positive study results have confirmed: usage of cultured unwanted microbiom would give rise to a reduction of acneic and maldor.

The overgrowth of P. acnes or Corynebacteria can aggravate acneic conditions and malodor. However, the described M. cochinch – inensis ingredient acts as a microbiota-regulating agent by selectively suppressing the growth of these unwanted species. The number of porphyrins, a measure of P. acnes colonization, was reduced as well as the number Coryneform bacteria, in

vitro and in vivo. This leads to a reduction in inflammatory spots and a normalized skin appearance. However, such reduction is not observed as permanent solutions; hygiene and dietary habits have been seen to be major contributors in adult giving rise to further work on a better permanent solution.

Reference:

1. R Sender et al, Revised estimates for the number of human and bacteria cells in the body PLOS Bio 14(8) e1002533 (2016) 


2. E Bianconi et al, An estimation of the number of cells in the human body, Ann Hum Bio 40(6) 463–71 (2013)

3. https://www.ncbi.nlm.nih.gov/pubmed/6602189

4. T.C. Scharschmidt et al., “A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes,” Immunity, doi:10.1016/j.immuni.2015.10.016, 2015.

5. EA Grice and JA Serge, The skin microbiome, Nat Rev Microbio 9(4) 244–53 (2011) 


6. N Schmidt and EH Gans, Tretinoin: A review of Its anti-inflammatory properties in the treatment of acne, J Clin and Aes Derm 4(11) 22–9 (2011) 


7. AA Adetutu et al, Studies on Staphylococcus aureus isolated from pimples, Pak J Biol Sci 20(7) 350–4 (2017)

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