Revolutionizing Modern Skin Care with an Old Technology: Phage Therapy in the Age of the Skin Microbiome
Podium 18
Presented by: Paul Lawrence
One of the major health concerns in the 21st century is the rise and proliferation of antibiotic resistant microbes. As the skin care industry pursues technologies that attempt to improve skin health through a modulation of the skin microbiome, it will be forced to contemplate the growing tide of ineffectual anti-microbials. Indeed, health care in general is currently facing a tsunami of resistance to such compounds that have up until now kept dangerous pathogens in check. Consequently, scientists across multiple disciplines have focused on the development of alternatives to antibiotics. One of the leading candidates to supplement and/or replace antibiotics is an approach known as “phage therapy”.
Bacteriophage-based therapy or “phage therapy” actually pre-dates the advent of anti-microbial compounds. Two doctors, Felix d’Herelle and Frederick Twort, from World War I stumbled upon materials infused with these viruses that uniquely target bacterial cells in a species-specific manner. While the rest of the world became infatuated with antibiotics and their ability to strike down the bacterial culprits of the worst diseases of the time, the former Soviet Union maintained an active phage therapy research program. Now, in the wake of growing antibiotic resistance, Western scientists have started collaborating with their Russian counterparts in resurrecting phage therapy for the rest of the globe. With an expanding understanding of how critical a balanced skin microbiome is to maintaining skin health, phage therapy represents a powerful new tool to exert changes in its microbial constituents.
We examined the utility of using phage therapy to counter acne vulgaris caused by the resident skin microbe Cutibacterium acnes. The capacity of three different bacteriophage preparations to individually target and eliminate C. acnes was evaluated in laboratory bacterial cultures using optical density measurements (at 600 nm) over a series of time points. This revealed that an inoculum of much less than one-tenth of the volume of the bacterial culture was sufficient to reduce the associated turbidity by greater than 75% in less than 24 hours. Although millions of years of evolution separate animal cells from the prokaryotic cells targeted by these phages, the potential cytotoxicity of the phages was tested on human keratinocytes and fibroblasts of which no negative effect was observed.
The aforementioned experiments illustrate the utility of this more-than-century old technology to modulate the skin microbiome in a targeted fashion. A reconstituted human epidermal model infused with C. acnes was employed to replicate blemish-prone skin and the three-phage cocktail was evaluated for its capacity to down-modulate the bacteria and reduce its inflammatory effects as well as to determine the most efficacious concentration to topically apply. The final outcome exceeded expectations where the phage cocktail showed no ill effects to the skin cells, effectively reduced the C. acnes population, and suppressed the associated inflammation.
Furthermore, the three-phage cocktail was examined for its compatibility in various topical formulations using the traditional plaque assay to determine efficacy. The findings from these experiments demonstrated that phage activity was substantially diminished in formulations containing high amounts of 1,3-propanediol. In contrast, water-based solutions containing phenoxyethanol or 1,2-alkanediol/hydroxyacetophenone had no negative impact on the capacity of the phage cocktail to eliminate its target bacteria.
In conclusion, phage therapy represents an exciting new methodology for modulating the skin microbiome in an effort to improve skin health. This platform is highly effective at reducing the targeted bacterial species without collateral damage to potentially beneficial neighboring species. The topical application of a formulation infused with the phage cocktail will deliver a one-two punch of countering one of the root causes of blemish-prone skin, while also repairing the damage inflicted by diminishing the levels of associated inflammatory mediators.
Bacteriophage-based therapy or “phage therapy” actually pre-dates the advent of anti-microbial compounds. Two doctors, Felix d’Herelle and Frederick Twort, from World War I stumbled upon materials infused with these viruses that uniquely target bacterial cells in a species-specific manner. While the rest of the world became infatuated with antibiotics and their ability to strike down the bacterial culprits of the worst diseases of the time, the former Soviet Union maintained an active phage therapy research program. Now, in the wake of growing antibiotic resistance, Western scientists have started collaborating with their Russian counterparts in resurrecting phage therapy for the rest of the globe. With an expanding understanding of how critical a balanced skin microbiome is to maintaining skin health, phage therapy represents a powerful new tool to exert changes in its microbial constituents.
We examined the utility of using phage therapy to counter acne vulgaris caused by the resident skin microbe Cutibacterium acnes. The capacity of three different bacteriophage preparations to individually target and eliminate C. acnes was evaluated in laboratory bacterial cultures using optical density measurements (at 600 nm) over a series of time points. This revealed that an inoculum of much less than one-tenth of the volume of the bacterial culture was sufficient to reduce the associated turbidity by greater than 75% in less than 24 hours. Although millions of years of evolution separate animal cells from the prokaryotic cells targeted by these phages, the potential cytotoxicity of the phages was tested on human keratinocytes and fibroblasts of which no negative effect was observed.
The aforementioned experiments illustrate the utility of this more-than-century old technology to modulate the skin microbiome in a targeted fashion. A reconstituted human epidermal model infused with C. acnes was employed to replicate blemish-prone skin and the three-phage cocktail was evaluated for its capacity to down-modulate the bacteria and reduce its inflammatory effects as well as to determine the most efficacious concentration to topically apply. The final outcome exceeded expectations where the phage cocktail showed no ill effects to the skin cells, effectively reduced the C. acnes population, and suppressed the associated inflammation.
Furthermore, the three-phage cocktail was examined for its compatibility in various topical formulations using the traditional plaque assay to determine efficacy. The findings from these experiments demonstrated that phage activity was substantially diminished in formulations containing high amounts of 1,3-propanediol. In contrast, water-based solutions containing phenoxyethanol or 1,2-alkanediol/hydroxyacetophenone had no negative impact on the capacity of the phage cocktail to eliminate its target bacteria.
In conclusion, phage therapy represents an exciting new methodology for modulating the skin microbiome in an effort to improve skin health. This platform is highly effective at reducing the targeted bacterial species without collateral damage to potentially beneficial neighboring species. The topical application of a formulation infused with the phage cocktail will deliver a one-two punch of countering one of the root causes of blemish-prone skin, while also repairing the damage inflicted by diminishing the levels of associated inflammatory mediators.