After recognizing the C acnes disease associations contributing to an acne microbiome, the logical next question asks how can we take advantage of this to target the skin microbiome for a beneficial therapeutic effect in acne. This is a new and exciting avenue of research that revolves around treatments with probiotics. Probiotics are defined as live microorganisms that when administered in adequate amounts may confer a health benefit on the host.14 The use of probiotics can be a targeted antimicrobial therapy. Specifically, certain C acnes could be reduced and others promoted. For example, healthy skin-associated C acnes phylotypes may be of use in a topical probiotic therapy or preventative regimen, designed to replace the acne-associated and other potentially opportunistic phylotypes.12 To date, there are no probiotic studies that have implemented this strategy of utilizing nonpathogenic strains of the same species of bacteria that share an ecological niche with their pathogenic counterparts. Other than bacteria, topical probiotics may also include C acnes bacteriophages, which are viruses that can lyse host bacteria. Investigations have already shown that C acnes bacteriophage lyse acne-associated and uncorrelated phylotypes, but they are often ineffective against healthy skin-associated phylotypes.15,16 Consequently, phages may also be utilized for highly specific strain replacement, and its formulation into a topical cream has already been demonstrated.17
Thus far, topical probiotic studies for the treatment of acne have been less selective in their choice of bacterial species. Several studies have shown that commensal bacteria like Staphylococcus epidermidis, Lactococcus, Lactobacillus, and Streptococcus species can directly inhibit C acnes growth via production of antimicrobial substances.18-22 Actual clinical trials utilizing a topical probiotic for the treatment of acne are few in number. A randomized, double blinded, phase 2b/3 study has demonstrated that application of a soil bacteria, Nitrosomonas eutropha, for 12 weeks led to a two-point reduction in an Investigator’s Global Assessment of acne severity compared with the control and a trend in the reduction of the number of inflammatory lesions.23 The results of a recent preprint show that twice-daily application of a cream containing a mixture of three different strains of Lactobacillus in patients with mild to moderate acne led to significant reduction in inflammatory lesions over an 8-week period.24 However, since these few clinical studies utilized species that do not naturally occur on the skin, a continued protective effect after discontinuing the treatment is unlikely. Future studies should rationally select for topical probiotics containing normal “healthy” skin commensals such as S epidermidis and especially healthy skin-associated phylotypes, which would allow for more specific strain replacement, minimize off-target effects, and enhance effectiveness and longevity of treatment.
Interestingly, modulation of the gut microbiome via oral probiotics has also been studied in patients with acne. The gut microbiome indirectly affects the skin; gut microbes have the ability to influence systemic inflammation, oxidative stress, and tissue lipid content.25 In fact, a recent clinical trial demonstrated the positive impact of an oral probiotic containing the gut commensal Lactobacillus paracasei on skin barrier function, supporting the link of this gut-skin axis.26 The few published studies in patients with acne support oral probiotic supplementation. One study compared an oral probiotic mixture of Lactobacillus acidophilus, Lactobacillus delbrueckii bulgaricus, and Bifidobacterium bifidum to minocycline therapy over 12 weeks. Both treatments yielded 67% lesion reduction, but the probiotic treatment was associated with fewer side effects.27 Another study revealed a 30% reduction in inflammatory lesions in patients with mild to moderate acne after daily consumption of fermented milk containing L bulgaricus and Streptococcus thermophilus for 12 weeks, though it should be noted that this study lacked a control.28 Another study showed significant improvement in appearance of back acne in patients that received oral Lactobacillus rhamnosus SP1 for 12 weeks compared with a placebo.29
In summary, the microbiome and host-microbiome interactions play an important role in acne. Thanks to recent genomic and metagenomic investigations, we now know that certain C acnes strains dominate in acne-affected skin. The emerging information on phenotypic and functional differences between members within the skin microflora offers new perspectives for the treatment of acne. Probiotics represent a microbiome-targeted therapeutic approach. However, more robust translational and clinical trials are needed to further characterize the skin microbiome in acne and the efficacy of probiotics in the treatment of the disease.
Dr Yu is a board-certified dermatologist and clinical instructor in the
division of dermatology, David Geffen School of Medicine, University of California, Los Angeles.
Disclosure: The author reports no relevant financial relationships.
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