Probiotics in Acne

Acne and the skin microbiome

Acne is one of the most common skin conditions with detrimental consequences for affected individuals. The pathophysiology of acne is not well understood.

The interactions of skin microbiome with the immune system of the body appears to be important, there is a perturbation, so called ‘dysbiosis’, in the composition and activities of the microbiota in acne.

New research in the acne onset

Staphylococcus epidermidis and Cutibacterium acnes are two major microbes of the skin that contribute to acne but they are also skin commensals that promote healthy skin by inhibiting growth and invasion of pathogens. C. acnes is involved in hydrolysis of triglycerides in sebum and release of fatty acids that are antimicrobial and contribute to an acidic pH of the skin surface. C. acnes is typically labeled as the etiological agent of acne – this outdated model of acne progression proposes that increased sebum production promotes over-proliferation of C. acnes in a plugged hair follicle, resulting in inflammation. New evidence indicates that C. acnes is equally present in follicles of acne and acne-free individuals. Recent advances in metagenomic sequencing of the acne microbiome show a diverse population structure that is distinct from healthy individuals; and the strains differ at the virulent-specific lineage level. There is a tight equilibrium between members of C. acnes phylotypes (subspecies) and within the other species in the development of acne. Direct visualisation of C. acnes in skin biopsies by immunofluorescence microscopy has revealed strong association of follicular C. acnes populations with acne. Highly complex C. acnes macrocolonies or ‘biofilms’ appear to be a more common in acne than normal skin and such structures could hinder sebum flow. As C. acnes is no longer seen as the sole culprit, the loss of the skin microbial diversity and the activation of the innate immunity might lead to this chronic inflammatory condition. Better characterisation of its phylogenetic cluster groups, their virulence and antimicrobial resistance of acne-associated strains is required.[i]

Newly emerging therapeutics

As people wish to use more natural treatments in dermatology, they look to complementary and alternative plant therapies for treatment. These are generally well tolerated but there are limited data with regard to efficacy and safety in terms of the specific ingredients, concentrations, and potential. These actives include plant oils and extracts (tea tree oil, barberry extract, green tea, basil oil, copaiba oil, resveratrol, rose water, seaweed), small molecules and minerals (niacinamide, gluconolactone, zinc), fish oil, ayurvedic treatments, dietary changes, biofeedback-assisted relaxation, cognitive imagery and acupuncture as well as probiotics that can manipulate the host microbiome and may confer health benefits for patients (in a form of lysates and/or live probiotics).[ii]

Probiotics: originally, live microorganism administered for the benefit of skin health, however dead intact bacteria and lysates (extracts) may also have probiotic properties.

Oral probiotics

The first clinical trial evaluating the effects of oral probiotics on acne was conducted almost 60 years ago using Lactobacillus strains and resulted in clinical improvement. Lacking a placebo control, the study only suggested a correlation in acne and metabolic processes of the intestinal tract. Nowadays, the gut-brain-skin axis posits mechanism to connect gastrointestinal health by oral probiotics to skin condition. Orally consumed pre and probiotics have been proven to reduce markers of oxidative stress, inflammation, and insulin resistance; they also regulate inflammatory cytokine release in the skin and improve skin barrier function and hydration. [iii] The emotions of stress (e.g., depression and anxiety), for instance, have been hypothesized to aggravate acne by altering the gut microbiota and increasing intestinal permeability, potentially contributing to skin inflammation and change in sebum production and fatty acid profiles.[iv][v]

Topical probiotics

The idea of using topical probiotics consisting of various bacterial formulations that will restore skin microbiome balance and selectively suppress pathogenic organisms and inflammation is a growing area of research for the treatment of acne. The concept of bacterial antagonism between C. acnes and S. epidermidis via fermentation was proposed, to develop topical probiotics against acne. Certain skin commensals can produce anti-inflammatory and antimicrobial metabolites under lipid-rich, hypoxic conditions that mimic the follicular environment. S. epidermidis can ferment glycerol, a natural constituent of triglycerides in sebum, to produce succinic acid which can inhibit the growth of C. acnes and suppress C. acnes-mediated inflammation (as proven in an animal model). A novel approach would be to exploit this interspecies competition and develop a live biologic topical agent containing a rationally selected commensal Staphylococcus strain with potent anti-C. acnes activity to treat acne lesions.[vi] To date, sucrose was proposed as a potentially novel treatment for the suppression of C. acnes growth via selectively augmenting fermentation by S. epidermidis. But also the use of commensal or health-associated lineages of C. acnes to reverse or modulate “acne dysbiosis” caused by specific type IA₁ strains; also, our understanding of the importance of C. acnes intra-species competition in shaping the community structure of this bacterium within the skin should be a prime target. Probiotic approaches to the treatment of acne may not prove straightforward since stable colonisation of donor bacteria is likely to be influenced by host genetics and other biological factors. Therefore, personalised probiotic therapies are likely to be required.[vii]

Commercial ventures for topical probiotic technologies

Topical probiotics have shown efficacy in a number of limited trials, however, their safety profiles, modes of action and therapeutic potential as well as regulatory gaps hinder commercialisation. This includes approval and classification of topical probiotic products by the FDA; currently there are no topical probiotic products the FDA has approved as drugs.

There is a lot of activity in the area of probiotics targeting skin microbiome in both topical and oral formulations to exploit these technologies in sensitive and ageing skin, psoriasis, eczema and eventually also in acne. L’Oreal, La Roche Posay, Merck, Pfizer and J&J have been involved in the skin microbiome research for some years now; topical technologies in this space range from lysates and inactive to live bacteria. A spin-off from the University of Manchester, SkinBioTherapeutics, is lining up partners to commercialize its SkinBiotix technology that uses Lactobacillus lysates for topical products for sensitive skin and eczema. Having signed an agreement with Croda, they will receive royalties on sales of products that result from the partnership, giving Sederma, a Croda subsidiary, an access to its science in return for access to cosmetic customers and a validated source of supply.[viii] Ingredient manufacturer Symrise, and the Swedish bioengineering company Probi are working together on probiotic-based cosmetic ingredients based on heat-treated Lactobacillus plantarum HEAL19 to strengthen the skin barrier in sensitive and dry skin[ix]. As skin barrier in acne prone skin types is also compromised, further opportunities for these technology platforms remain to be explored.

As acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis, and current treatments are focused to act on C. acnes only, both these microbes can be explored as therapy. Royal DSM has signed an agreement with Belgian life sciences start-up S-Biomedic to develop and commercialise a skin care active that uses probiotic technology (C. acnes) to treat acne.[x] Also probiotics derived from S. epidermidis can restore the naturally balanced microbiota or through targeting the regulation of the host’s response. The beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation has been proven.[xi][xii] Capitalising on this research, Bayer plans to develop selected strains for new skincare products under a future licensing agreement with Azitra, using their proprietary platform technology of S. epidermidis strains to identify potential candidates for the treatment of acne. Each species has a unique spectrum of characteristics e.g. inhibiting keratin adhesion, organic acid production, or biofilm formation[xiii].

The ‘skin-microbiome-targeting’ topical probiotics offer a promising platform for the development and commercialization of new products that appeal to consumers. It is imperative that these new developments invest heavily in science-based solutions and multi-disciplinary research partnerships.

References

[i] Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

[ii] A review of diagnosis and treatment of acne in adult female patients

[iii] Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris

[iv] Potential Role of the Microbiome in Acne: A Comprehensive Review

[v] Acne vulgaris, probiotics and the gut-brain-skin axis – back to the future?

[vi] Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris

[vii] Propionibacterium acnes and Acne Vulgaris: New Insights from the Integration of Population Genetic, Multi-Omic, Biochemical and Host-Microbe Studies

[viii] SkinBioTherapeutics harnesses gut bacteria to address $100B skin care market

[ix] Symrise works with bioengineering company Probi on probiotic-based cosmetic ingredients

[x] ‘Strategic’ microbiome move: DSM signs probiotic tech agreement with S-Biomedic

[xi] Staphylococcus epidermidis: A Potential New Player in the Physiopathology of Acne?