A Diverse Mosaic: The Facial Skin Microbiome

Personal care impacts skin health and quality of life, an invaluable asset still often undervalued. Understanding the intricacies of skin microbiome has become a challenge for the scientific community driven by consumers’ increasing demand for microbiome friendly skincare. In this blog, NBIC’s Senior Innovation Consultant, Dr Katerina Steventon, discusses the importance of hydration, area-specific diversity, dysbiosis and the rising prevalence of acne during the pandemic.

Biofilms and skincare

In facial skincare, biofilms are associated with skin conditions (such as acne and atopic dermatitis) and can contribute to the cause or inhibit the effectiveness of treatment. The reasons consumers purchase personal care products are not consciously associated with prevention and control of biofilms but linked to skin hygiene, facial aesthetics and wellbeing.

Biofilms have been implicated in acne. Even if the traditional model of acne pathology relates primarily to follicular plug (due to ‘sticky epithelial cells’ and increased sebum production), with the deep follicular anaerobic environment favouring Cutibacterium acnes and inflammation, biofilms are more prevalent in acne patients. C.acnes biofilms can adhere to the pilosebaceous unit due to mucopolysaccharide matrix capable of binding to lipid surfaces, and thus aggravate acne severity or inhibit the bioavailability of medication.[i] Whilst the regulatory definition of cosmetics is limited to ‘cleaning, changing the appearance of, protecting and keeping skin in good condition”[ii], prevention of mild acne – spots and blemishes, is well within the remit of personal care. The adverse impact of acne on quality of life has been clearly accepted by society.

Sebum and hydration: predictors of microbial growth in different facial areas

The majority of skin microbes populate the stratum corneum, the desquamating outermost layer of the skin. This layer in the face is thin; with unique functional characteristics e.g., sebum production and relatively poor barrier function (often with subclinical inflammation) compared to the skin of the body. There are differences in biophysical parameters of the stratum corneum on the forehead, cheek, nose and perioral regions. The forehead is more sebaceous than the cheek; the so-called T-zone of the face, comprising the forehead and nose and the chin, has higher levels of sebum than other facial regions.

The skin microbiome varies across individuals. In healthy women, 1000 microbial genera have been identified in the face; predominantly Cutibacterium (58.6%), Staphylococcus, Streptococcus, Corynebacterium and Paracoccus. In normal skin, the nature and diversity of facial resident skin microbiome is a function of lipid and water content of the stratum corneum in a specific area of the face. Indian research has shown that cheek sebum content is the most significant predictor of microbiome composition and diversity. Increase in cheek sebum causes an increase in the prevalence of Cutibacterium and reduced microbiome diversity.

The skin microflora maintains homoeostasis by cross-talk with the host innate immune system and modulates microbial growth by production of antimicrobial peptides; thus protecting the host from infectious pathogens. Imbalance (dysbiosis) in the skin microbiome alters skin health and is linked to acne. Sebum and hydration vary both across individuals – and across different areas of the face inviting site-specific skin microbiome profiles.

Ethnic and area-specific diversity

There are considerable differences in composition, diversity and temporal variability of the skin microbiota between Asian and Western populations. In Caucasians, these microbiome signatures have been characterised and considerable topographical and temporal variance across dry, moist and sebaceous areas are understood. Correlating inter-individual differences in microbiome profiles with differences in sebum and hydration levels is complex; research should take into consideration skin hydration and sebum production changes with age, hormonal status and season, etc. Comparing Indian and Dutch Caucasian populations, the proportions of the most abundant phyla are similar. In terms of genera, differences in Corynebacterium (India: 3.6%; The Netherlands: 7.7%) and Streptococcus (India: 4.0%; The Netherlands: 0.8%) were reported. These ethnic differences may have implication in understanding differences in prevalence of acne. Dr Riccardo Sfriso, Lead Scientist Skin Microbiome, R&D Personal Care & Aroma at DSM Nutritional Products Ltd said,

“Compared to the overall body skin surface, facial skin represents only a small area. However, facial skin is extremely complex and consists e.g. of dry areas (such as the cheek) and oily areas (known as T-zone). Besides its heterogeneity, facial skin and its microbiota are constantly exposed to external factors, such us UV light, pollution, constant changes in temperature and relative humidity. Facial stratum corneum is generally thinner compared to most other body sites, has more immature corneocytes and an impaired barrier function. Its stratum disjunctum is diminished due to elevated proteolytic activity. In the past years, we impressively demonstrated and visualized vast gradients of biophysical properties (TEWL, hydration and pH) within short distances on the face. These suggest a differential microbial colonization. As a confirmation of this hypothesis, our recent facial microbiome study performed on Caucasians revealed interesting insights. One of them concerns the different spatial distribution of the most abundant species on facial skin, the Cutibacterium acnes. C. acnes was found to be present in its highest abundance on the forehead, the oiliest area, whereas it reached its lowest abundance on the cheek, the driest facial site. In addition, the second most abundant bacterium, S. epidermidis was found to establish its highest relative abundance on the chin”.

Dysbiosis as a function of skin changes

In past research, Cutibacterium has been reported as the most abundant bacterium in the sebaceous areas and Corynebacterium in the well-hydrated skin. The Indian study confirmed that cheek sebum concentration is strongly linked with microbial composition and diversity (sebum changes on the highly sebaceous forehead do not alter significantly to impact on bacterial abundances). Cutibacterium was the most abundant genus whose frequency increased with rising sebum production in the cheek. As a commensal, the C.acnes binds to oleic acid of the sebum, which in turn facilitates co-aggregation at sebaceous sites and metabolizes fatty acids to propionic and acetic acid to eradicate of harmful species. Only some strains of C.acnes are associated with acne inflammation (we have explored the role of C.acnes in skin health in our previous publication[iii]). C.acnes also synthesizes proteases with detrimental effect on other commensal and/or pathogenic strains explaining reduction of microbial diversity with increase in cheek sebum concentration. Dr Andrew McDowell PhD, FHEA, Lecturer in Molecular Microbiology at Ulster University said,

“In the majority of adults, large and relatively stable populations of the anaerobic bacterium C. acnes dominate the microbiota within the pilosebaceous follicles and surface of sebum-rich areas of the skin. These populations help to maintain skin health via the production of various molecules that inhibit the growth of more pathogenic microbes. Despite the normally positive relationship that we share with C. acnes, the bacterium does have a darker side due to its widely described association with the inflammatory skin disease acne vulgaris, and possibly the depigmenting skin condition progressive macular hypomelanosis; the organism has also been linked to infections beyond the skin. While inflammatory acne has previously been thought to arise as a result of C. acnes overgrowth in response to heighted sebum production during adolescence, recent research indicates this view is incorrect. The disease is now believed to occur, in part, due to an imbalance or loss of C. acnes strain type diversity on the skin and the dominance of particular lineages with an apparent heightened capacity to drive acne progression through specific interactions with the host. This improved understanding of the acne disease process has now opened up new opportunities in the development of acne therapeutics based on skin microbiome modulation”.

In contrast, when skin is well-hydrated, the environment facilitates growth and changes in abundances of specific bacterial taxa. Therefore, hydration level on the forehead is the next best predictor of nature and diversity of facial skin microbiome (the change in cheek hydration in young women may not alter significantly enough to impact on the change in bacterial abundance). No change in Corynebacterium was reported with changing sebum or hydration levels of the facial skin; instead Streptococcus and Haemophilus are significantly associated with sebum cheek and forehead hydration. Corynebacterium helps in maintenance of skin health (a nitrogen fixing coryneform it hydrolyzes urea from sweat to ammonia, which serves as a nitrogen source for other cutaneous microbes). In contrast, rise in Streptococcus and Haemophilus can be linked to skin infections.

Though considerable temporal variability of the microbiome membership and structure has been observed in the past[iv] prompting the proposal of a personalized pattern, an Indian study has shown microbiome patterns with temporal stability at both the phylum and genus. Quantitative levels of sebum and hydration in specific areas of facial skin are strongly associated with the distribution of specific bacterial taxa inhabiting the stratum corneum. Except for Cutibacterium and Streptococcus, all the other genera associated with changes in sebum and hydration levels, yet maintained temporal stability over time, belong to rare taxa. It seems that rare taxa help in maintaining an overall microbial community structure and this confirmation of the link to host factors is indicative of their functional importance.[v]

It is this lack of temporal variability that leads some industry experts to conclude that healthy skin microbiome remains largely unchanged in time – even when subjected to daily washing, a range of temperature, humidity and pollution, exposure to antimicrobials and stress, etc., and it does not warrant an intervention. However, skin health is hard to define and acne-prone skin with compromised skin barrier would benefit from a microbiome imbalance correcting intervention.

Rising prevalence of acne in the pandemic

The prevalence of adverse skin reactions have risen during the pandemic, perhaps due to extreme hand hygiene, stress in the daily lives and the compulsory wearing of face masks. Masks are essential for COVID-19 prevention but they can modify facial skin microenvironment and trigger the onset of skin conditions; acne as the most prevalent followed by facial rashes and itch. Material, duration of wear (more than 4 hours/day) and reuse of face masks play a role.[vi] Also, patients with acne wearing masks for at least 6 h/day for 6 weeks displayed an increased severity of the condition in mask-related areas.[vii]

Inoculation with habitual touch

Frequent touching of mouth and nose is normal, yet in times of a pandemic this indirect contact plays perhaps an underestimated role in transmission in some respiratory and skin infections beyond Covid-19.  Face-touching can transfer microorganisms between surfaces to mucosa leading to self-inoculation and transmission of infections. The variation of microbial distribution on human skin could be aided by self-touch inoculation. Research in China has shown that students touched mucous membranes of their lips, nose and eyes on average 34.3 times per hour, mainly with their non-dominant hand.[viii] In another study, students touched their face on average 23 times per hour. Of all face touches, 44% involved contact with a mucous membrane; the mouth being the most frequent, followed by the nose and eyes.[ix] In stressful times, students may use these unconscious gestures to self-soothe.

Facial skin microbiome research has to conquer yet another layer of complexity. The face is highly exposed to the external environment with skin having specific, often fragile, characteristics. The face is prone to unconscious touch transmission; the touch centres around the communication triangle of the face – the mouth, nose and the eyes, targeting the skin of the oily T-zone. This transmission can aggravate skin conditions by inducing microbial imbalance and perhaps even biofilm formation in the sebum-rich follicular environment.

The facial microbiome field, researchers and developers may well face additional challenges in the future as both societal trends and the environment influence further the pressures to be met.

References

[i] Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial

[ii]Regulation (ec) no 1223/2009 of the European parliament and of the council of 30 November 2009 on cosmetic products

[iii] C. acnes Assist: Evolving Skin Care for Changing Needs, A Commentary*

[iv] Temporal variability is a personalized feature of the human microbiome

[v] Sebum and Hydration Levels in Specific Regions of Human Face Significantly Predict the Nature and Diversity of Facial Skin Microbiome

[vi] The Effects of the Face Mask on the Skin Underneath: A Prospective Survey During the COVID-19 Pandemic

[vii] COVID-19 related masks increase severity of both acne (maskne) and rosacea (mask rosacea): Multi-center, real-life, telemedical, and observational prospective study

[viii] Most self-touches are with the nondominant hand

[ix] P157: Face-touching: a frequent habit for self-inoculation of transmissible infections?

Dr Katerina Steventon, NBIC Senior Innovation Consultant