The immunomodulatory potential of phage therapy to treat acne: a review on bacterial lysis and immunomodulation

BACKGROUND: Characterized by an inflammatory pathogenesis, acne is the most common skin disorder worldwide. Altered sebum production, abnormal proliferation of keratinocytes, and microbiota dysbiosis represented by disbalance in Cutibacterium acnes population structure, have a synergic effect on inflammation of acne-compromised skin. Although the role of C. acnes as a single factor in acne development is still under debate, it is known that skin and skin-resident immune cells recognize this bacterium and produce inflammatory markers as a result. Control of the inflammatory response is frequently the target for acne treatment, using diverse chemical or physical agents including antibiotics. However, some of these treatments have side effects that compromise patient adherence and drug safety and in the case of antibiotics, it has been reported C. acnes resistance to these molecules. Phage therapy is an alternative to treat antibiotic-resistant bacterial strains and have been recently proposed as an immunomodulatory therapy. Here, we explore this perspective about phage therapy for acne, considering the potential immunomodulatory role of phages. METHODOLOGY: Literature review was performed using four different databases (Europe PubMed Central-ePMC, Google Scholar, PubMed, and ScienceDirect). Articles were ordered and selected according to their year of publication, number of citations, and quartile of the publishing journal. RESULTS: The use of lytic bacteriophages to control bacterial infections has proven its promising results, and anti-inflammatory effects have been found for some bacteriophages and phage therapy. These effects can be related to bacterial elimination or direct interaction with immune cells that result in the regulation of pro-inflammatory cytokines. Studies on C. acnes bacteriophages have investigated their lytic activity, genomic structure, and stability on different matrices. However, studies exploring the potential of immunomodulation of these bacteriophages are still scarce. CONCLUSIONS: C. acnes bacteriophages, as well as other phages, may have direct immunomodulatory effects that are yet to be fully elucidated. To our knowledge, to the date that this review was written, there are only two studies that investigate anti-inflammatory properties for C. acnes bacteriophages. In those studies, it has been evidenced reduction of pro-inflammatory response to C. acnes inoculation in mice after bacteriophage application. Nevertheless, these studies were conducted in mice, and the interaction with the immune response was not described. Phage therapy to treat acne can be a suitable therapeutic alternative to C. acnes control, which in turn can aid to restore the skin’s balance of microbiota. By controlling C. acnes colonization, C. acnes bacteriophages can reduce inflammatory reactions triggered by this bacterium.