536
J. Cosmet. Sci., 75.6, 536–552 (November/December 2024)
*Address all correspondence to Paul Lawrence, paul.lawrence@biocogent.com
Reviving a More Than Century-Old Technology for Modern
Skincare
PAUL LAWRENCE, BRIANNA SCACCHI, KIMBERLY DEW AND JOSEPH CECCOLI
Biocogent, Stony Brook, New York, USA (P.L., B.S., K.D., J.C.)
Accepted for publication August 2, 2024. Presented at SCC76 and recipient of 2023 Hans Schaeffer Award.
Synopsis
Research into the skin microbiome continues to accelerate at an unrelenting pace with an expanded
understanding of how these microbial constituents contribute to skin health. The largest group of these microbes
is the bacterial component which includes both beneficial and potentially problematic microorganisms. Some
of these exhibit dual roles of commensalism and antagonism with regard to maintaining healthy skin, and
as such, skin microbiome modulation efforts should be balanced and precise. To that end, interest has been
rekindled in a technology that dates back more than a century, so-called “bacteriophage therapy.” This entails
using the natural predators of bacteria in the environment to diminish their population levels viruses (or
bacteriophages) that exclusively target bacteria in a species-specific and sometimes strain-specific manner.
Here, we present the results of an investigation into using a collection of bacteriophages to target and diminish
the levels of Cutibacterium acnes, a member of the skin microbiome that can contribute to the development
of acne vulgaris. The bacteriophage cocktail successfully diminished specifically C. acnes both in vitro and
in vivo with no adverse effects detected. As other topical microbiome modulatory ingredients exhibit more
nonspecific antimicrobial effects on the skin microbiota, this approach offers an attractive, highly targeted
alternative.
INTRODUCTION
Our understanding of the significant contribution of the skin microbiome to overall skin
health rapidly increases with each passing day. Currently, the skin microbiome is one of the
most discussed new areas of skin care research—how the various microbial inhabitants of
the skin (skin microbiota) contribute to the pathogenesis of many skin diseases and disorders.
Indeed, the skin supports a rich community of microorganisms that includes bacteria,
fungi, archaea, protists, and viruses.1 Many of these microbes are considered commensals
as their habitation of the skin prevents the encroachment of pathogenic microorganisms.
Two of the most abundant bacterial species are the Gram-positives: Cutibacterium acnes and
Staphylococcus epidermidis.2 The former has been established to contribute to the “acid mantle”
of the skin that keeps many harmful microbes from getting a foothold through the action
of lipases that it secretes.3 The latter species secretes an enzyme called sphingomyelinase
that promotes the production of ceramides that reinforce the skin barrier.4

537 Modern Skincare
The largest constituent of this vast microbial community are the bacteria, which have
been implicated in many skin conditions. The skin bacteriome can vary considerably
depending upon which region of the skin is examined giving rise to the study of the
“skin biogeography” where specific groups and species of bacteria have been identified
that prefer dry, moist, and sebaceous landscapes.1,5,6 For example, S. epidermidis has been
found to be abundant in moist regions, while the curiously anaerobic C. acnes exhibits a
preference for the oily, sebaceous sites. Indeed, C. acnes establishes colonies deep inside
the pilosebaceous units of the skin, where the bacteria construct stratified biofilms and
promote sebum production to be insulated from atmospheric oxygen impeding growth.7
Fluctuations in the homeostatic levels of these various microorganisms are referred to as
a “dysbiosis,” and many skin conditions have been attributed to diminished or excessive
growth of specific members of the microbiota. One such example is the case of increased
growth of Staphylococcus aureus, sometimes at the expense of S. epidermidis, contributing to
the incidence of atopic dermatitis.8,9 Similarly, although the precise molecular pathogenesis
remains to be delineated, and as the name suggests, C. acnes has been suggested to play a
key role in the development of acne vulgaris.3,10,11
Acne vulgaris is a fairly widespread skin disease afflicting adolescents and adults from
around the world inflicting both physiological and psychological stress on the individual.12–14
The classical model of C. acnes involvement in the pathogenesis of blemished skin suggests
that higher than normal growth of the bacteria leads to excessive sebum production and
induction of various inflammatory pathways.15 Other groups have reported evidence that
different strains of C. acnes are more likely to promote “acneic” conditions than others.11
Unfortunately, to date, the various proposed models do not account for all incidence of
acne in people, thus warranting further investigations into the microbiological component
of this skin disease.
Skin microbiome research has progressed from the early days where its scope was limited to
only those microbes that were “culturable” off the skin. The advent of 16S ribosomal RNA
(rRNA) sequencing allowed for “non-culturable” species to be identified and characterized.16
More recently, metagenomic sequencing has expanded our knowledge of the skin microbiota
beyond traditional bacteria to include archaea, fungi, protists, and viruses.1,17,18 Modern
skincare has sought to leverage these findings to deliver innovative topical solutions to
modulate and balance the skin microbiome for beneficial outcomes. However, given the
complexity of these interrelationships and the evidence that many of these microorganisms
make positive contributions to skin health, the need for precise, targeted interventions
becomes more apparent. To that end, the application of bacteriophage (literally “bacteria
consuming”) therapy, a technology dating back more than 100 years, provides an avenue
for skincare scientists to navigate that delicate balance.19–22 The precision of this approach
stems from the exquisite species-specificity (sometimes strain-specificity) exhibited by
naturally occurring bacteriophages for their bacterial targets. These bacterial viruses
recognize and attach to specific bacteria via unique molecules decorating their surfaces.23
For example, motifs within cell wall teichoic acids displayed on the thick peptidoglycan
(murein) cell walls of most Gram-positive bacteria are a common binding site for the
cognate bacteriophages of many skin-resident bacteria, including C. acnes and S. aureus.24
Once anchored to the surface of the bacterium, the bacteriophage will puncture the cell
wall and inject their nucleic acid genome (most commonly deoxyribonucleic acid [DNA])
inside, which thereupon will initiate a replication cycle that often terminates in the rupture
of the bacterial cell. This mode of bacteria destruction is what captured the attention