Acne, the Skin Microbiome, and Antibiotic Treatment

Introduction

Acne vulgaris (i.e., acne) is a chronic inflammatory condition of the skin affecting an estimated 20.5% of the global population (Saurat et al., 2024) at a rate that has steadily increased over the last few decades from 8563.4 per 100 000 population in 1990 to 9790.5 per 100 000 population in 2021 among those aged 10 - 24 years (Zhu et al., 2024). Pathogenesis of this skin disorder has been linked to hyper-production of sebum, abnormal production and shedding of skin cells that causes blockage of hair follicles, and host inflammatory responses.

Recent evidence also points to the influence of skin-associated microorganisms in triggering onset of this disease. The bacterium Cutibacterium acnes inhabits the lipid-rich environment of sebaceous glands, and can be considered either a skin commensal or pathogen depending on specific strain (Niedźwiedzka et al., 2024), with much evidence demonstrating a strong association between the proliferation of certain C. acnes strains and the stimulation of multiple inflammatory pathways that exacerbate acne symptoms (Dreno et al., 2024).

The conventional approach to combating acne is through administration of antibiotics like macrolides, clindamycin, and tetracyclines that are active on C. acnes at the expense of depleting the rest of the skin microbiome. These treatments can be administered either orally or topically, with the former producing anti-inflammatory effects and latter possessing more direct antimicrobial properties. However, increasing global incidences of antibiotic resistance among some strains as the result of frequent and long-term use of these treatments has led to concerns over the sustainability of such approaches, and has broached discussion into the development of alternative anti-acne therapies.

This review article sought to summarise recent studies looking at skin microbiome dynamics in acne while assessing the effectiveness of antibiotic treatment in combating this disorder as a way to better understand the relationship between acne, microbiome, and antibiotics. It also explored the potential of novel non-antibiotic therapies in effectively combating growth of acne-associated bacteria (Xu and Li, 2019).

Results

Long-term use of macrolides has facilitated the increased emergence of macrolide-resistant C. acnes strains, with resistance to macrolides such as erythromycin and azithromycin reaching over 50% (Walsh, Efthimiou and Dréno, 2016) and up to 100% (Sardana et al., 2016), respectively, in some studies. Similar effects have been in clindamycin, with strain resistance increasing from 4% in 1999 (Kurokawa, Nishijima and Kawabata, 1999) to 90.4% in 2016 (Sardana et al., 2016) and some reports emerging of up to 52% of acne patients carrying at least one strain of clindamycin-resistant C. acnes (Lomholt and Kilian, 2014). 

Similarly, prolonged and excessive use of other antibiotics such as tetracyclines has reportedly also led to a rise in C. acnes resistance up to 30% across different geographical regions. Even after termination of antibiotic treatment, resistant strains may still continue to persist on the skin for a long while after, leading to the possible recurrence of acne and reduced efficacy of any future treatments to alleviate the condition (Xu and Li, 2019). 

Other groups of skin bacteria have also demonstrated resistance to macrolide and clindamycin classes of antibiotics, with 30% of Staphylococcus epidermidis isolates from acne patients showing resistance to erythromycin, roxithromycin, and clindamycin. There have also been reports of correlation in resistance between different species of antibiotic bacteria on the skin, with more than 80 % of patients carrying clindamycin-resistant C. acnes also carrying strains of clindamycin-resistant S. epidermidis in one study (Nakase et al., 2014). 

While the effects of tetracyclines on skin bacteria other than C. acnes has not been as thoroughly investigated, some evidence points to the efficacy of new members of tetracyclines, like lymecyclin, in acne treatment. One study demonstrated a decrease in clinical acne grades and the relative abundance of Cutibacterium on the cheeks of acne patients after 6 weeks of lymecyclin treatment. However, the relative abundance of other groups like Streptococcus, Staphylococcus, Micrococcus, and Corynebacterium increased (Kelhälä et al., 2017).

Some suggested solutions to reduce the emergence of antibiotic resistance includes combining topical antibiotics with benzoyl peroxide (BPO), an antimicrobial agent that can aid in reducing the total number of C. acnes bacteria and rates of antimicrobial resistance by maximising the amount of bacteria killed (Walsh, Efthimiou and Dréno, 2016), thus reducing the probability of any cells remaining and developing resistance post-antibiotic administration (Xu and Li, 2019).

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

Future Directions

Other potential therapy areas beyond traditional antibiotic approaches are currently being developed to mitigate the effects of acne. One such solution that has been proposed is the use of vaccines targeting the Christie-Atkins-Munch-Petersen (CAMP) factor of C. acnes bacteria, with more clinical research required before their development (Kim and Kim, 2024).

Biologic treatments that involve targeting and inhibiting specific signalling proteins involved in acne-related inflammation have shown promise in reducing these symptoms. These include inhibitors such as adalimumab and secukinumab (Kim and Kim, 2024).

Designed antimicrobial peptides (dAMPs) are a novel class of therapeutics that could also be used in the future for direct targeting of acne-associated C. acnes that have already developed resistance to antibiotics to control symptoms of acne (Kim and Kim, 2024).

Conclusions

Antibiotics are the most common treatment against acne that work by eradicating acne-associated species of bacteria, usually C. acnes that can trigger or exacerbate symptoms of disease. The rapid emergence of antibiotic resistance in members of the resident skin microbiota has made the development of alternative solutions that treat acne while reducing the global burden of resistance a critical goal for microbe-related disease research. Several alternatives that are currently being looked into include combining antibiotic use with topical antimicrobial agents like BPO, potential vaccination targets, and even microbiome-associated therapies (Xu and Li, 2019).

Current data on the effects of several other antibiotics that may be used for the treatment of acne such as trimethoprim–sulfamethoxazole, levofloxacin, rifampin, dapsone, and metronidazole remains sparse. Future studies investigating these will help address knowledge gaps regarding the efficacy of these antibiotics in treating acne, as well as their sensitivity. Additionally, future longitudinal studies on the long-term use of alternative therapies for the treatment of acne will provide further information on how they modulate skin microbiome composition, dynamics, and overall acne symptoms within cutaneous communities (Xu and Li, 2019).

References

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