How to manage and influence the skin microbiome
New approaches to the skin microbiome have evolved over recent years; the industry started to view ‘the microbial layer’ as the most outer layer of our body e.g. the Givaudan-termed ‘Stratum microbium™’ and acknowledged the importance of bacteria on the skin, renaming stratum corneum as ‘Stratum Ecologica’ in 2019. In his article, Dr J. M. Crowther argues that the stratum corneum is a layer that cannot be perceived as dead; it supports complex ecosystems, vast intricate feedback loops, with a delicate interplay between the skin itself and the microbiome.
The dialogue with our eco-system
Despite the complexity of research in this area, and having discussed dysbiotic microbiome shifts and diversity in our previous blogs, taking into account the environment we live in as a whole makes sense. When in contact with other people, e.g. players[i] during contact sport, skin microbiomes have been shown to overlap after tournament. Dog-ownership[ii] can increase the sharing of microbes and direct, frequent contact with our cohabitants (humans and pets) can significantly shape the composition of our skin microbiome. By now we have understood that only the superficial epidermal microbiota, described as a “microbial fingerprint”, is unique to the individual, and depends on their lifestyle and genetic predisposition. The deeper dermal microbiota is universal to healthy people, functionally distinct and in direct contact with the immune response of our body.
Granularity in innovation trends
In their Q2 2020 review, DSM[iii] confirm that ‘Skin microbiome requires new approaches due to the structural complexity of the skin and relatively small microbial concentrations’. Biotech and personal care companies are targeting skin microbiome to address both healthy skin and skin conditions. Observing technology trends, Deanna Utroske, Editor at Cosmetics Design, has highlighted five nuanced approaches to innovation in personal care early in 2020, that add granularity to the umbrella claims of ‘microbiome friendly’ and ‘microflora balancing’ products. Adding Lactobacilli sp. (first microbe we encounter after birth), quorum-quenching strategies (that limit quorum sensing communication and, therefore, bacterial virulence), introducing a post-biotic into the environment (to care for skin microbiome per se, rather than the skin itself), new developments in pre-, pro- and post-biotic innovation by indie brands e.g. AOBiome and Chinese brand AO+ Skincare [iv] and last but not least, developing proprietary bacterial strains.[v]
Treatment of skin conditions
Skin conditions are relatively common. Acne affects 9.4% of the global population and the prevalence of atopic dermatitis reached in 20% of children and up to 3% of adults[vi][vii] with the trends continuing to rise. Skin conditions are associated with skin microbiome shift and a colonization by pathogens, yet it is still not clear whether microbiome imbalance leads to skin pathologies, or underlying skin conditions negatively impacting on the microbial equilibrium. There is a range of microbiome impacting technologies on offer as traditional antimicrobials are implicated in the damage to the skin, disturbance of the microbiome, and contribution to the development of antimicrobial resistance. Using a combination approach, TBH Skincare, an Australian company target biofilms in acne; by using citric acid and sodium citrate dehydrate to break down extracellular polymeric substance and inhibit it from reforming and a salt benzalkonium chloride, to kill bacteria by dehydration and producing an osmotic shock agents or agents that would act only on specific bacteria and help to re-normalise the microbiome are deemed beneficial. Using a probiotic, a commensal bacterial strain already present on the skin, engineering bacteria to modify their beneficial capabilities or using bacteriophage has been explored in skin conditions. Dr Timofey Skvortsov, a Lecturer in Microbial Bioinformatics at the School of Pharmacy, Queen’s University Belfast, advised on application of phage technology for the skin microbiome,
“Bacteriophages (phages) are harmless bacterial viruses ubiquitous and environment friendly, that can efficiently and specifically kill detrimental bacteria without affecting the rest of skin microbiota present. Purified phage lytic enzymes (lysins) are usually more stable than whole phages and can be used instead. In terms of new technology applications, research by British company Fixed-Phage Ltd shows that a cream containing phage active against C. acnes completely eliminated all pathogenic bacteria from skin surface within an hour. Recently a Californian company, Ellis Day Skin Science, introduced a new product with Cutiphage™, a cocktail of two C. acnes phages.[viii] The Dutch company Micreos raised €30 Million to continue development of their phage lysin based Gladskin skin care product for eczema”.[ix]
In probiotics in acne, proprietary Cutibacterium acnes strains are the target. Naked Biome use a less health-associated C. acnes strain (called MBO1) with low inflammatory potential, in phase 1b clinical trial, twice-daily MBO1 treatments for 12 weeks showed a microbial shift towards MBO1’s genotype and a trend towards fewer inflammatory lesions. S-Biomedic (in collaboration with J&J[viii]) focus on products incorporating C. acnes strain producing low levels of linoleic acid isomerase, an enzyme implicated in acne. Xycrobe Therapeutics have engineered strains of C. acnes to produce an anti-inflammatory cytokine, interleukin-10 (IL-10), reduced in people with acne.[ix]
In advancement of eczema treatment with commensal Staphylococci species, MatriSys Biosciences treat atopic dermatitis using a bacterium S. hominis and Azitra, supported by Bayer, produced a strain of S. epidermis to outcompete the pathogenic S. aureus.[x]
How to monetise the science
Whether the companies follow a faster route to commercialisation as a consumer product or a rather long path of a therapeutic is a matter of strategy – taking into account regulatory requirements, time/cost implications, volume versus premium pricing and the likely return on investment. The development of skin microbiome-regulating products and technologies is a promising endeavour, a number of dermatology and cosmetic companies have shown strong commercial interest in skin microbiome startups. Interviewed for a publication in Nature, Eric de La Fortelle, a partner at Seventure Partners, a Paris-based venture capital firm in the life sciences, says,
“Most companies are grappling with how to balance cosmetic and therapeutic interests. It’s not unusual that the same bacterial strains can be applied to either sorts of uses. The only difference is that therapeutic applications generally rely on higher doses that engraft better into skin and persist for longer durations”.
The research partnerships are at early stages, yet in a year or so if published results show a proof of efficacy, ‘everyone will rally for investment to follow and boost the field’.[xi]
Dr Katerina Steventon, NBIC Senior Innovation Consultant