Treatment response to isotretinoin correlates with specific shifts in Cutibacterium acnes strain composition within the follicular microbiome

Zachary T. Nolan, Kalins Banerjee, Zhaoyuan Cong, Samantha L. Gettle, Amy L. Longenecker, Yuka I. Kawasawa, Andrea L. Zaenglein, Diane M. Thiboutot, George W. Agak, Xiang Zhan, Amanda M. Nelson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


There are no drugs as effective as isotretinoin for acne. 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. We determined how the follicular microbiome changes with isotretinoin and identified which alterations correlate with a successful treatment response. Whole genome sequencing was done on casts from facial follicles of acne patients sampled before, during and after isotretinoin treatment. Alterations in the microbiome were assessed and correlated with treatment response at 20 weeks as defined as a 2-grade improvement in global assessment score. We investigated the α-diversity, β-diversity, relative abundance of individual taxa, Cutibacterium acnes strain composition and bacterial metabolic profiles with a computational approach. We found that increased β-diversity of the microbiome coincides with a successful treatment response to isotretinoin at 20 weeks. Isotretinoin selectively altered C. acnes strain diversity in SLST A and D clusters, with increased diversity in D1 strains correlating with a successful clinical response. Isotretinoin significantly decreased the prevalence of KEGG Ontology (KO) terms associated with four distinct metabolic pathways inferring that follicular microbes may have limited capacity for growth or survival following treatment. Importantly, these alterations in microbial composition or metabolic profiles were not observed in patients that failed to achieve a successful response at 20 weeks. Alternative approaches to recapitulate this shift in the balance of C. acnes strains and microbiome metabolic function within the follicle may be beneficial in the future treatment of acne.

Original languageEnglish (US)
Pages (from-to)955-964
Number of pages10
JournalExperimental Dermatology
Issue number7
StatePublished - Jul 2023

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology


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