The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities

Acne vulgaris is a prevalent condition impacting seborrheic (oily) areas of the body such as the face, chest, and back. Its onset has been linked to a myriad of factors from excess sebum production, follicular hyperkeratinization (i.e., abnormally rapid production and shedding of skin cells causing blockage of sebaceous hair follicles), and host inflammatory responses (Niedźwiedzka et al., 2024).

The skin resident bacterium Cutibacterium acnes (formerly known as Propionibacterium acnes) is another factor of interest; its involvement in various infections of the skin has led to its discovery as an opportunistic pathogen that likely plays a role in acne pathogenesis. The pathogenicity of these particular acne-causing strains is likely related to their ability to form biofilms and produce pro-inflammatory enzymes that worsen acne symptoms, as not all C. acnes strains produce these effects and many actively contribute to maintaining skin microbiome balance and homeostasis (Niedźwiedzka et al., 2024).

Similar disruptions to skin microbiome balance have also been noted to be caused by conventional acne treatments like oral antibiotics, benzoyl peroxide, and topical retinoids targeting C. acnes for removal. This has produced a demand for alternative, microbiome-friendly therapeutic approaches that reduce severity of acne symptoms while maintaining and restoring microbiome balance (Niedźwiedzka et al., 2024).

This review sought to provide a comprehensive overview of the current state of research in traditional and emerging treatments to combat acne, including the potential of microbiome-targeted therapies such as probiotics and phage treatment as an alternative to conventional antibiotic-based approaches. It also explored the dynamic between different skin pathogen populations, and how they might be able to influence one another’s susceptibility to treatment (Niedźwiedzka et al., 2024).

Results

Among affecting C. acnes bacteria, use of antibiotics has also increased rates of resistance in other resident skin microbiome species such as S. epidermidis, another common group found on the skin, with one study reporting high resistance rates of S. epidermidis acne isolates to an array of antibiotics like tetracycline (31%), doxycycline (27%), clindamycin (33%), and erythromycin (58%) (Moon et al., 2012). 

Other studies on C. acnes biofilm formation report the ability of these microbial structures to enhance susceptibility to antibiotics for other groups of bacteria, with reduced size and restricted formation of Staphylococcus aureus (another skin pathogen) biofilms being observed upon exposure to these bacteria. These S. aureus biofilms exhibited increased susceptibility to multiple antibiotics such as ciprofloxacin and rifampicin upon C. acnes exposure, presenting interesting implications for the efficacy of antibiotic treatments during skin pathobiont coinfection (Abbott et al., 2022).

Some of the global effects of antibiotic use beyond treating skin may extend to influencing gut microbiome composition, with previous studies reporting significant disruptions to gut microbiome structure during antibiotic use. Sarecycline had the most minimal impact, allowing bacterial populations to recover after treatment, while minocycline depleted multiple beneficial groups such as Lactobacillus, Ruminococcaceae and Clostridiaceae that managed to only partially recover post-treatment (Moura et al., 2022). Similar disruptions have been linked to the onset of gastrointestinal disorders like irritable bowel disease, demonstrating the importance of considering whole body effects when administering antibiotic acne treatments.

Probiotics represent an alternative emerging therapy area for the treatment of acne without antibiotics. Topical probiotic formulations consisting of beneficial bacterial species such as Lactobacillus and Bifidobacterium are capable of increasing skin ceramide production, reducing inflammation, and improving skin barrier function against pathogens to improve acne symptoms and promote microbiome health and skin immunity. They have also demonstrated significant efficacy in reducing the growth of acne-associated bacteria like C. acnes, showing potential as a treatment for symptoms of acne.

Topical probiotic formulations like SkinDuo™ containing the strain Lactiplantibacillus plantarum LP01 have shown significant efficacy in reducing the growth of acne associated bacteria like C. acnes and S. epidermidis, as well as a reduction in the production of inflammatory markers such as IL-1α, IL-6, and IL-8 that worsen the appearance of acne lesions, as well as significantly reducing lipid production (Podrini et al., 2023).

Oral probiotics containing Lacticaseibacillus rhamnosus and Arthrospira platensis were capable of reducing the number of lesions on the skin of patients in one clinical trial, with a greater proportion of patients receiving probiotic treatment demonstrating a reduction in both total and non-inflammatory acne lesions compared to the placebo group. The probiotic treatment also reduced the overall severity of acne in patients (Eguren et al., 2024). 

Phage therapy is another emergent treatment that seeks to reduce the severity of acne by harnessing the power of viruses known as bacteriophages (or, phages) that specifically infect bacterial cells. This makes them an ideal candidate for acne therapy, as they offer the option of targeting only acne-associated pathogenic C. acnes strains without disrupting the overall balance of the skin microbiome, unlike many broad-spectrum antibiotics that indiscriminately target both harmful and beneficial bacteria. A recent preclinical study investigating the effectiveness of this treatment found that topical application of C. acnes-targeting phages resulted in a marked reduction of bacterial load and inflammation in C. acnes-induced acne-like lesions (Rimon et al., 2023), demonstrating the potential for this type of phage therapy to act as either adjunct or alternative to existing antibiotic approaches combating symptoms of acne (Niedźwiedzka et al., 2024).

Table summarising the effects of various acne treatments on the skin microbiome

Future Directions

Another bioactive approach that is currently emerging as a potential therapy for acne treatment is the use of prebiotic compounds that selectively promote the growth of certain beneficial strains or species of bacteria on the skin by providing key nutrients. Current prebiotics of interest include fructooligosaccharides (FOS) and galactooligosaccharides (GOS) (Niedźwiedzka et al., 2024).

Synbiotics (the combination of probiotics and prebiotics) also present an emerging area of research. These work by boosting the activity of beneficial microbes while providing essential nutrients for their growth, indicating a potential synergistic approach to managing acne symptoms (Niedźwiedzka et al., 2024).

Therapeutic formulations containing beneficial CRISPR-possessing bacteria may be used to restore balance to the skin microbiome by competing with pathogenic strains of C. acnes to reduce their abundance, as well as inhibiting any bacteriophage-induced inflammation on the skin that could worsen acne symptoms or further disbalance the skin microbial community (Maguire and McGee, 2024).

Conclusion

Beyond traditional antibiotic treatments combating acne, several emergent bioactive approaches are currently being developed with promising results for reducing both the severity of acne, as well as targeting the dysbiotic mechanisms potentially underlying its pathogenesis. These offer more personalised and sustainable solutions for both acne therapy, and also the growing concern of antibiotic resistance within skin-associated microbiomes (Niedźwiedzka et al., 2024).

More research is still needed to better understand the influence and interactions of different microbial communities beyond bacteria on the skin such as fungi and viruses, and how this might impact upon traditional and alternative acne therapies in the long term as a way to facilitate the development of more effective microbiome-based treatments for acne (Niedźwiedzka et al., 2024). Continued research into clinical trials for probiotics and phage therapies will also be necessary to help determine the most effective formulations, dosages, and methods of application for their integration into conventional acne treatment procedures (Niedźwiedzka et al., 2024).

References

Abbott, C. et al. (2022) ‘Cutibacterium acnes biofilm forming clinical isolates modify the formation and structure of Staphylococcus aureus biofilms, increasing their susceptibility to antibiotics’, Anaerobe, 76, p. 102580. Available at: https://doi.org/10.1016/j.anaerobe.2022.102580.

Eguren, C., Navarro-Blasco, A., Corral-Forteza, M., Reolid-Pérez, A., Setó-Torrent, N., García-Navarro, A., Prieto-Merino, D., Núñez-Delegido, E., Sánchez-Pellicer, P. and Navarro-López, V. (2024). A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris. Acta Dermato-Venereologica, [online] 104, pp.adv33206–adv33206. doi:https://doi.org/10.2340/actadv.v104.33206.

Maguire, G. and McGee, S.T. (2024). NeoGenesis MB-1 with CRISPR Technology Reduces the Effects of the Viruses (Phages) Associated with Acne - Case Report. Integrative medicine (Encinitas, Calif.), [online] 23(4), pp.34–38. Available at: https://pubmed.ncbi.nlm.nih.gov/39355416/.

Moon, S.H. et al. (2012) ‘Antibiotic resistance of microbial strains isolated from Korean acne patients’, The Journal of Dermatology, 39(10), pp. 833–837. Available at: https://doi.org/10.1111/j.1346-8138.2012.01626.x.

Moura, I.B. et al. (2022) ‘Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota’, Frontiers in Microbiology, 13. Available at: https://doi.org/10.3389/fmicb.2022.901911.

Niedźwiedzka, A. et al. (2024) ‘The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities’, International Journal of Molecular Sciences, 25(21), p. 11422. Available at: https://doi.org/10.3390/ijms252111422.

Podrini, C., Schramm, L., Marianantoni, G., Apolinarska, J., McGuckin, C., Forraz, N., Milet, C., Desroches, A.-L., Payen, P., D’Aguanno, M. and Biazzo, M. (2023). Topical Administration of Lactiplantibacillus plantarum (SkinDuoTM) Serum Improves Anti-Acne Properties. Microorganisms, [online] 11(2), p.417. doi:https://doi.org/10.3390/microorganisms11020417.

Rimon, A. et al. (2023) ‘Topical phage therapy in a mouse model of Cutibacterium acnes-induced acne-like lesions’, Nature Communications, 14(1), p. 1005. Available at: https://doi.org/10.1038/s41467-023-36694-8.