Microbial Diversity Leads to Successful Isotretinoin Response in Acne

In patients with acne, isotretinoin proved to be more effective in those with increased skin microbiome diversity.

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In a recent pilot, longitudinal cohort study,¹ researchers sought to determine the drug’s efficacy as it relates to certain aspects of, or changes in, the skin’s microbiome. Additionally, they intended to better understand isotretinoin’s impact on pathogenic factors of acne.

“There are no drugs as effective as isotretinoin for acne,” study authors wrote. “Deciphering the changes in the microbiome induced by isotretinoin in the pilosebaceous follicle of successfully treated patients can pave the way to identify novel therapeutic alternatives.”

15 participants were diagnosed with moderate to severe acne by a dermatologist and fully completed the study. Prior to receiving treatment, researchers collected samples of facial pilosebaceous follicles from each participant in order to perform wholegenome sequencing. Additionally, all participants underwent a 1-month antibiotic and 2-week benzoyl peroxide washout prior to beginning treatment. None of the participants had a prior history of isotretinoin use.

Each week, a dermatologist assessed participants’ acne disease severity in accordance with the Investigator’s Global Assessment (IGA) scale.

During the first month of treatment, all participants were treated with 0.5 mg/kg of isotretinoin per day. Upon the completion of the first month of the study, this dosage was increased to 1 mg/kg/day until the conclusion of the 20-week study.

Throughout the study, researchers continued to collect samples and perform sequencing at weeks 1, 4, 8, and 20. Additionally, they collected a final sample and performed sequencing at 6 months post study conclusion from 9 participants.

In order for patients to have a successful treatment response, researchers sought a minimum 2-point reduction in IGA score by week 20. Participants were considered “responders” or “slow responders” based on their treatment response at 20 weeks.

However, despite the study’s 20-week timeline, all participants were treated until acne was cleared. This period ranged from 5 to 10 months.

By the conclusion of the 20 weeks, 11 of the 15 participants were deemed “responders” based on a 2-point IGA score improvement.

In addition to researchers’ examination of efficacy, researchers also assessed α- and β-diversity using Bray-Curtisdissimilarity and Shannon Diversity Index.

In responders, β-diversity had significantly increased at 20 weeks. Additionally, researchers found that isotretinoin use decreased the overall abundance of cutibacterium acnes (C. acnes) while also shifting the diversity of C. acnes strains.

“We report that a successful clinical response at Week 20 coincides with an increase in the β-diversity of the microbiome, a selective decrease in the relative abundance of C. acnes and alterations in C. acnes strain diversity,” study authors wrote. “Furthermore, the microbial metabolic pathways associated with growth and energy metabolism were suppressed. Importantly, our study revealed that isotretinoin induces specific changes in the microbiome of the pilosebaceous follicle that are associated with a successful treatment outcome.”

Reference

1. Nolan ZT, Banerjee K, Cong Z, et al. Treatment response to isotretinoin correlates with specific shifts in cutibacterium acnes strain composition within the follicular microbiome. Experimental Dermatol. 2023. doi:10.1111/exd.14798